4-72283389-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_014243.3(ADAMTS3):c.3365G>A(p.Ser1122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000882 in 1,613,748 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014243.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS3 | NM_014243.3 | c.3365G>A | p.Ser1122Asn | missense_variant | Exon 22 of 22 | ENST00000286657.10 | NP_055058.2 | |
ADAMTS3 | XM_011532421.2 | c.3308G>A | p.Ser1103Asn | missense_variant | Exon 22 of 22 | XP_011530723.1 | ||
ADAMTS3 | XM_011532422.4 | c.3281G>A | p.Ser1094Asn | missense_variant | Exon 22 of 22 | XP_011530724.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000579 AC: 88AN: 152110Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00169 AC: 423AN: 250912Hom.: 7 AF XY: 0.00223 AC XY: 303AN XY: 135576
GnomAD4 exome AF: 0.000914 AC: 1336AN: 1461520Hom.: 13 Cov.: 31 AF XY: 0.00125 AC XY: 910AN XY: 727010
GnomAD4 genome AF: 0.000572 AC: 87AN: 152228Hom.: 2 Cov.: 32 AF XY: 0.000672 AC XY: 50AN XY: 74414
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.3365G>A (p.S1122N) alteration is located in exon 22 (coding exon 22) of the ADAMTS3 gene. This alteration results from a G to A substitution at nucleotide position 3365, causing the serine (S) at amino acid position 1122 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
ADAMTS3-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
ADAMTS3: BP4, BS1, BS2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at