chr9-18635982-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001040272.6(ADAMTSL1):c.641A>G(p.His214Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000586 in 1,449,464 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000059 ( 0 hom. )
Consequence
ADAMTSL1
NM_001040272.6 missense
NM_001040272.6 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 6.29
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTSL1 | NM_001040272.6 | c.641A>G | p.His214Arg | missense_variant | 6/29 | ENST00000380548.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTSL1 | ENST00000380548.9 | c.641A>G | p.His214Arg | missense_variant | 6/29 | 5 | NM_001040272.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000169 AC: 4AN: 236642Hom.: 0 AF XY: 0.0000234 AC XY: 3AN XY: 128334
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GnomAD4 exome AF: 0.0000586 AC: 85AN: 1449464Hom.: 0 Cov.: 30 AF XY: 0.0000569 AC XY: 41AN XY: 720996
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2023 | The c.641A>G (p.H214R) alteration is located in exon 6 (coding exon 6) of the ADAMTSL1 gene. This alteration results from a A to G substitution at nucleotide position 641, causing the histidine (H) at amino acid position 214 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;D;N
REVEL
Benign
Sift
Benign
T;D;T;T
Sift4G
Benign
T;T;T;T
Polyphen
P;.;B;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0202);Gain of MoRF binding (P = 0.0202);Gain of MoRF binding (P = 0.0202);Gain of MoRF binding (P = 0.0202);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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