chr15-78811214-C-T

Variant names:

• chr15-78811214-C-T
• rs979460265
• NM_014272.5:c.7G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014272.5(ADAMTS7):​c.7G>A​(p.Gly3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,228,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000093 (1 hom.)
• Consequence: ADAMTS7 NM_014272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.06
• 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]

MORF4L1 (HGNC:16989): (mortality factor 4 like 1) Enables protein N-terminus binding activity. Involved in double-strand break repair via homologous recombination and histone modification. Located in nuclear speck. Part of NuA4 histone acetyltransferase complex and Sin3 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05234158).

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.7G>A	p.Gly3Ser	missense	Exon 1 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.7G>A	p.Gly3Ser	missense	Exon 1 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.7G>A	p.Gly3Ser	missense	Exon 1 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972107.1		c.7G>A	p.Gly3Ser	missense	Exon 1 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152044 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

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: 0.000956

GnomAD4 exome AF: 0.00000929 AC: 10 AN: 1075992 Hom.: 1 Cov.: 31 AF XY: 0.00000197 AC XY: 1 AN XY: 508046

African (AFR) AF: 0.00 AC: 0 AN: 22744

American (AMR) AF: 0.000965 AC: 8 AN: 8290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14174

East Asian (EAS) AF: 0.00 AC: 0 AN: 26328

South Asian (SAS) AF: 0.00 AC: 0 AN: 19464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2894

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 917620

Other (OTH) AF: 0.0000461 AC: 2 AN: 43394

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152150 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74390

African (AFR) AF: 0.00 AC: 0 AN: 41538

American (AMR) AF: 0.000785 AC: 12 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000204

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	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.8
DANN	Benign	0.91
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.011
Sift	Benign	0.33	T
Sift4G	Benign	0.23	T
Polyphen		0.0030	B
Vest4		0.082
MutPred		0.33		Gain of glycosylation at G3 (P = 0.002)
MVP		0.23
MPC		0.19
ClinPred		0.049	T
GERP RS		-3.8
PromoterAI		-0.031	Neutral
Varity_R		0.073
gMVP		0.28

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: rs979460265; hg19: chr15-79103556;