rs374281685

Variant names:

• chr15-78762430-C-T
• rs374281685
• NM_014272.5:c.4876G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78762430-C-T
• chr15-78762430-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014272.5(ADAMTS7):​c.4876G>A​(p.Glu1626Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000368 in 1,521,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (1 hom.)
• Consequence: ADAMTS7 NM_014272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101769745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS7	NM_014272.5	MANE Select	c.4876G>A	p.Glu1626Lys	missense	Exon 23 of 24	NP_055087.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS7	ENST00000388820.5	TSL:1 MANE Select	c.4876G>A	p.Glu1626Lys	missense	Exon 23 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.4849G>A	p.Glu1617Lys	missense	Exon 23 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972107.1		c.4816G>A	p.Glu1606Lys	missense	Exon 23 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000381 AC: 6 AN: 157390 AF XY: 0.0000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000913

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000570

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000380 AC: 52 AN: 1369482 Hom.: 1 Cov.: 30 AF XY: 0.0000310 AC XY: 21 AN XY: 676430

African (AFR) AF: 0.00 AC: 0 AN: 29650

American (AMR) AF: 0.000150 AC: 5 AN: 33434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21838

East Asian (EAS) AF: 0.00 AC: 0 AN: 34960

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4054

European-Non Finnish (NFE) AF: 0.0000413 AC: 44 AN: 1066576

Other (OTH) AF: 0.0000356 AC: 2 AN: 56154

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74494

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.0000332 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.73	N
PhyloP100		4.2
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.048
Sift	Benign	0.069	T
Sift4G	Uncertain	0.014	D
Polyphen		0.32	B
Vest4		0.13
MVP		0.53
MPC		0.23
ClinPred		0.17	T
GERP RS		3.5
Varity_R		0.051
gMVP		0.29
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374281685; hg19: chr15-79054772;