NM_014272.5:c.4891G>T

Variant names:

• chr15-78762415-C-A
• rs150570920
• NM_014272.5:c.4891G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014272.5(ADAMTS7):​c.4891G>T​(p.Val1631Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,488,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1631I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: ADAMTS7 NM_014272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07013729).

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.4891G>T	p.Val1631Phe	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.4891G>T	p.Val1631Phe	missense	Exon 23 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.4864G>T	p.Val1622Phe	missense	Exon 23 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972107.1		c.4831G>T	p.Val1611Phe	missense	Exon 23 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000145 AC: 2 AN: 137612 AF XY: 0.00

Gnomad AFR exome AF: 0.000104

Gnomad AMR exome AF: 0.0000532

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000973 AC: 13 AN: 1336442 Hom.: 0 Cov.: 30 AF XY: 0.00000609 AC XY: 4 AN XY: 657182

African (AFR) AF: 0.000385 AC: 11 AN: 28592

American (AMR) AF: 0.0000339 AC: 1 AN: 29484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20374

East Asian (EAS) AF: 0.00 AC: 0 AN: 33714

South Asian (SAS) AF: 0.00 AC: 0 AN: 68692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3788

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048624

Other (OTH) AF: 0.0000183 AC: 1 AN: 54582

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74364

African (AFR) AF: 0.0000724 AC: 3 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ESP6500AA AF: 0.000230 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000831 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.58
DANN	Benign	0.94
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.12
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.085
Sift	Benign	0.72	T
Sift4G	Uncertain	0.049	D
Polyphen		0.69	P
Vest4		0.24
MVP		0.088
MPC		0.29
ClinPred		0.037	T
GERP RS		-8.2
Varity_R		0.039
gMVP		0.27
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs150570920; hg19: chr15-79054757;