chr6-105101099-T-C

Position:

• chr6-105101099-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199563.2(BVES):​c.1073A>G​(p.Gln358Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BVES NM_001199563.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.238

Genes affected

BVES (HGNC:1152): (blood vessel epicardial substance) This gene encodes a member of the POP family of proteins containing three putative transmembrane domains. This gene is expressed in cardiac and skeletal muscle and may play an important role in development of these tissues. The mouse ortholog may be involved in the regeneration of adult skeletal muscle and may act as a cell adhesion molecule in coronary vasculogenesis. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03348455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BVES	NM_001199563.2	c.1073A>G	p.Gln358Arg	missense_variant	8/8	ENST00000314641.10	NP_001186492.1
BVES	NM_007073.4	c.1073A>G	p.Gln358Arg	missense_variant	8/8		NP_009004.2
BVES	NM_147147.4	c.1073A>G	p.Gln358Arg	missense_variant	8/8		NP_671488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BVES	ENST00000314641.10	c.1073A>G	p.Gln358Arg	missense_variant	8/8	1	NM_001199563.2	ENSP00000313172.5
BVES	ENST00000336775.9	c.1073A>G	p.Gln358Arg	missense_variant	8/8	1		ENSP00000337259.5
BVES	ENST00000446408.2	c.1073A>G	p.Gln358Arg	missense_variant	8/8	1		ENSP00000397310.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2X Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Oct 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.8
DANN	Benign	0.89
DEOGEN2	Benign	0.035	T;T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.32	.;.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.033	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.18	N;N;N
REVEL	Benign	0.013
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.69	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.062
MutPred		0.23		Loss of ubiquitination at K355 (P = 0.0317);Loss of ubiquitination at K355 (P = 0.0317);Loss of ubiquitination at K355 (P = 0.0317);
MVP		0.081
MPC		0.26
ClinPred		0.021	T
GERP RS		1.3
Varity_R		0.061
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-105548974;