chr9-18622276-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001040272.6(ADAMTSL1):c.508G>A(p.Val170Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00241 in 1,613,976 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 9 hom. )
Consequence
ADAMTSL1
NM_001040272.6 missense
NM_001040272.6 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.87
Genes affected
ADAMTSL1 (HGNC:14632): (ADAMTS like 1) This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0058428645).
BP6
Variant 9-18622276-G-A is Benign according to our data. Variant chr9-18622276-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3042672.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTSL1 | NM_001040272.6 | c.508G>A | p.Val170Ile | missense_variant | 5/29 | ENST00000380548.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTSL1 | ENST00000380548.9 | c.508G>A | p.Val170Ile | missense_variant | 5/29 | 5 | NM_001040272.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00218 AC: 331AN: 152144Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00262 AC: 657AN: 250822Hom.: 0 AF XY: 0.00291 AC XY: 395AN XY: 135512
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GnomAD4 exome AF: 0.00243 AC: 3555AN: 1461714Hom.: 9 Cov.: 31 AF XY: 0.00259 AC XY: 1885AN XY: 727154
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GnomAD4 genome AF: 0.00217 AC: 331AN: 152262Hom.: 1 Cov.: 32 AF XY: 0.00228 AC XY: 170AN XY: 74434
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ADAMTSL1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 25, 2022 | 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). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L;L
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;.;.;B;.
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at