rs35702995
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000187.4(HGD):c.260A>C(p.Glu87Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000729 in 1,598,508 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000187.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00386 AC: 588AN: 152186Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.000836 AC: 210AN: 251280Hom.: 3 AF XY: 0.000560 AC XY: 76AN XY: 135790
GnomAD4 exome AF: 0.000398 AC: 575AN: 1446204Hom.: 6 Cov.: 26 AF XY: 0.000330 AC XY: 238AN XY: 720550
GnomAD4 genome AF: 0.00387 AC: 590AN: 152304Hom.: 3 Cov.: 33 AF XY: 0.00361 AC XY: 269AN XY: 74472
ClinVar
Submissions by phenotype
Alkaptonuria Pathogenic:1Benign:2
The variant was originally described in AKU patient in PMID:19862842. It has been submitted to the HGD gene mutation database as polymorphism, however, predictions using HGDiscovery (https://biosig.lab.uq.edu.au/hgdiscovery/) indicate protomer destabilization and hexamer disruption, thus, it is most likely pathogenic (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00129). -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at