chr15-78759509-G-A

Variant names:

• chr15-78759509-G-A
• rs2055006904
• NM_014272.5:c.4973C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014272.5(ADAMTS7):​c.4973C>T​(p.Pro1658Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000689 in 1,596,994 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: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ADAMTS7 NM_014272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3769697).

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.4973C>T	p.Pro1658Leu	missense	Exon 24 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.4973C>T	p.Pro1658Leu	missense	Exon 24 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.4946C>T	p.Pro1649Leu	missense	Exon 24 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972107.1		c.4913C>T	p.Pro1638Leu	missense	Exon 24 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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

GnomAD4 exome AF: 0.00000623 AC: 9 AN: 1444782 Hom.: 0 Cov.: 34 AF XY: 0.00000417 AC XY: 3 AN XY: 718614

African (AFR) AF: 0.00 AC: 0 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.00 AC: 0 AN: 85312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4112

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1109190

Other (OTH) AF: 0.00 AC: 0 AN: 59776

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.0000482 AC: 2 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

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: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T
Eigen	Benign	0.039
Eigen_PC	Benign	-0.076
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.23
Sift	Benign	0.041	D
Sift4G	Benign	0.12	T
Polyphen		0.95	P
Vest4		0.28
MutPred		0.29		Gain of MoRF binding (P = 0.0633)
MVP		0.47
MPC		0.55
ClinPred		0.98	D
GERP RS		2.9
Varity_R		0.18
gMVP		0.52
Mutation Taster		=78/22	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: rs2055006904; hg19: chr15-79051851;