chr15-78764056-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014272.5(ADAMTS7):c.4463A>G(p.Gln1488Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000577 in 1,385,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000058 ( 0 hom. )
Consequence
ADAMTS7
NM_014272.5 missense
NM_014272.5 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.78
Genes affected
ADAMTS7 (HGNC:223): (ADAM metallopeptidase with thrombospondin type 1 motif 7) The protein encoded by this gene is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family. Members of this family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs and may regulate vascular smooth muscle cell (VSMC) migration. Mutations in this gene may be associated with susceptibility to coronary artery disease. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.35358998).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS7 | NM_014272.5 | c.4463A>G | p.Gln1488Arg | missense_variant | 21/24 | ENST00000388820.5 | |
ADAMTS7 | XM_047432122.1 | c.4463A>G | p.Gln1488Arg | missense_variant | 21/24 | ||
ADAMTS7 | XM_047432123.1 | c.3704A>G | p.Gln1235Arg | missense_variant | 20/23 | ||
ADAMTS7 | XM_011521166.3 | c.2717A>G | p.Gln906Arg | missense_variant | 10/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS7 | ENST00000388820.5 | c.4463A>G | p.Gln1488Arg | missense_variant | 21/24 | 1 | NM_014272.5 | P1 | |
ADAMTS7 | ENST00000569934.1 | n.603A>G | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD3 exomes AF: 0.00000683 AC: 1AN: 146430Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 77842
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GnomAD4 exome AF: 0.00000577 AC: 8AN: 1385580Hom.: 0 Cov.: 31 AF XY: 0.00000587 AC XY: 4AN XY: 681850
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
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 | Jun 09, 2022 | The c.4463A>G (p.Q1488R) alteration is located in exon 21 (coding exon 21) of the ADAMTS7 gene. This alteration results from a A to G substitution at nucleotide position 4463, causing the glutamine (Q) at amino acid position 1488 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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0249);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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