ClinVar Miner

Submissions for variant NM_022168.4(IFIH1):c.457G>T (p.Ala153Ser)

dbSNP: rs781431529
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767992 SCV000898747 uncertain significance Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 2017-10-19 criteria provided, single submitter clinical testing IFIH1 NM_022168.3 exon 2 p.Ala153Ser (c.457G>T): This variant has not been reported in the literature but is present in 1/30460 South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs781431529). This variant Serine (Ser) is present in >20 species including mammals, and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV000767992 SCV003512450 uncertain significance Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 153 of the IFIH1 protein (p.Ala153Ser). This variant is present in population databases (rs781431529, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with IFIH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 625960). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224410 SCV003920046 uncertain significance Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7; Immunodeficiency 95 2021-03-30 criteria provided, single submitter clinical testing IFIH1 NM_022168 exon 2 p.Ala153Ser (c.457G>T): This variant has not been reported in the literature but is present in 1/30460 South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs781431529). This variant Serine (Ser) is present in >20 species including mammals, and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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