ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.762T>A (p.Pro254=) (rs201478438)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767098 SCV000535126 uncertain significance not provided 2017-01-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The synonymous P254P (c.762 T>A) variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, and no homozygous individuals have been reported. The P254P (c.762 T>A) variant occurs at nucleotide position that is conserved through mammals. Although in silico splice algorithms do not predict that this change results in abnormal gene splicing, the physiological consequence of this variant cannot be precisely determined in the absence of functional mRNA studies.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Integrated Genetics/Laboratory Corporation of America RCV000445066 SCV000864085 uncertain significance not specified 2017-01-03 criteria provided, single submitter clinical testing Variant summary: The ALMS1 c.759T>A (p.Pro253Pro, alternative name c.762T>A) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 10/120720 control chromosomes at a frequency of 0.0000828, which does not exceed the estimated maximal expected allele frequency of a pathogenic ALMS1 variant (0.0022361). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign.
Invitae RCV000470100 SCV000554295 likely benign Alstrom syndrome 2016-04-16 criteria provided, single submitter clinical testing

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