ClinVar Miner

Submissions for variant NM_001128.6(AP1G1):c.44G>A (p.Arg15Gln)

dbSNP: rs2145525235
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV001728059 SCV002764680 pathogenic Usmani-Riazuddin syndrome, autosomal dominant 2020-09-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002539779 SCV003542939 uncertain significance Inborn genetic diseases 2021-07-12 criteria provided, single submitter clinical testing The c.44G>A (p.R15Q) alteration is located in exon 2 (coding exon 1) of the AP1G1 gene. This alteration results from a G to A substitution at nucleotide position 44, causing the arginine (R) at amino acid position 15 to be replaced by a glutamine (Q). Based on data from the Genome Aggregation Database (gnomAD), the AP1G1 c.44G>A alteration was not observed, with coverage at this position. This alteration has been observed to occur de novo in a patient presenting with developmental delay, intellectual disability, truncal hypotonia, lumbar hyperlordosis, behavioral issues, short fingers, and bilateral 2-3 toe syndactyly (Usmani, 2021). This amino acid position is highly conserved in available vertebrate species. The in silico prediction for the p.R15Q alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
3billion RCV001728059 SCV004013718 pathogenic Usmani-Riazuddin syndrome, autosomal dominant criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 34102099). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001299367 / PMID: 34102099). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
OMIM RCV001728059 SCV001976488 pathogenic Usmani-Riazuddin syndrome, autosomal dominant 2021-10-04 no assertion criteria provided literature only

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