3-64686662-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_182920.2(ADAMTS9):c.422C>A(p.Ser141Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_182920.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251366Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135862
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727228
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2023 | The c.422C>A (p.S141Y) alteration is located in exon 2 (coding exon 2) of the ADAMTS9 gene. This alteration results from a C to A substitution at nucleotide position 422, causing the serine (S) at amino acid position 141 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 13, 2024 | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 141 of the ADAMTS9 protein (p.Ser141Tyr). This variant is present in population databases (rs746670316, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ADAMTS9-related conditions. ClinVar contains an entry for this variant (Variation ID: 1349467). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at