15-78762432-G-A

Variant names:

• chr15-78762432-G-A
• NM_014272.5:c.4874C>T

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.4874C>T​(p.Thr1625Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTS7 NM_014272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090155244).

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.4874C>T	p.Thr1625Ile	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.4874C>T	p.Thr1625Ile	missense	Exon 23 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.4847C>T	p.Thr1616Ile	missense	Exon 23 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972107.1		c.4814C>T	p.Thr1605Ile	missense	Exon 23 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000145 AC: 2 AN: 1380634 Hom.: 0 Cov.: 30 AF XY: 0.00000293 AC XY: 2 AN XY: 682692

African (AFR) AF: 0.00 AC: 0 AN: 30138

American (AMR) AF: 0.00 AC: 0 AN: 35244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22388

East Asian (EAS) AF: 0.00 AC: 0 AN: 35292

South Asian (SAS) AF: 0.00 AC: 0 AN: 74876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4140

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1072008

Other (OTH) AF: 0.0000176 AC: 1 AN: 56726

GnomAD4 genome Cov.: 33

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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.3
DANN	Benign	0.92
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.051
Sift	Benign	0.21	T
Sift4G	Benign	0.47	T
Polyphen		0.0040	B
Vest4		0.13
MutPred		0.23		Loss of phosphorylation at T1625 (P = 0.0063)
MVP		0.26
MPC		0.20
ClinPred		0.16	T
GERP RS		3.5
Varity_R		0.041
gMVP		0.17
Mutation Taster		=93/7	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

hg19: chr15-79054774;