chr15-78762430-C-A

Variant names:

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

Variant summary

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

The NM_014272.5(ADAMTS7):​c.4876G>T​(p.Glu1626*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000146 in 1,369,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ADAMTS7 NM_014272.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Glu1626*	stop_gained	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>T	p.Glu1626*	stop_gained	Exon 23 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.4849G>T	p.Glu1617*	stop_gained	Exon 23 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972107.1		c.4816G>T	p.Glu1606*	stop_gained	Exon 23 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1369482 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 676430

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

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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: 0.00000188 AC: 2 AN: 1066576

Other (OTH) AF: 0.00 AC: 0 AN: 56154

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.82	D
PhyloP100		4.2
Vest4		0.28
GERP RS		3.5
Mutation Taster		=17/183	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;