6-105115749-A-T

Position:

• chr6-105115749-A-T

Variant summary

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

The NM_001199563.2(BVES):​c.895T>A​(p.Ser299Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BVES NM_001199563.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89

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=0.04214418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BVES	NM_001199563.2	c.895T>A	p.Ser299Thr	missense_variant	7/8	ENST00000314641.10	NP_001186492.1
BVES	NM_007073.4	c.895T>A	p.Ser299Thr	missense_variant	7/8		NP_009004.2
BVES	NM_147147.4	c.895T>A	p.Ser299Thr	missense_variant	7/8		NP_671488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BVES	ENST00000314641.10	c.895T>A	p.Ser299Thr	missense_variant	7/8	1	NM_001199563.2	ENSP00000313172.5
BVES	ENST00000336775.9	c.895T>A	p.Ser299Thr	missense_variant	7/8	1		ENSP00000337259.5
BVES	ENST00000446408.2	c.895T>A	p.Ser299Thr	missense_variant	7/8	1		ENSP00000397310.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2024

The c.895T>A (p.S299T) alteration is located in exon 7 (coding exon 6) of the BVES gene. This alteration results from a T to A substitution at nucleotide position 895, causing the serine (S) at amino acid position 299 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.54
DEOGEN2	Benign	0.037	T;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.090
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.72	.;.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.042	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.97	L;L;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.81	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.12
MutPred		0.17		Loss of phosphorylation at S299 (P = 0.0621);Loss of phosphorylation at S299 (P = 0.0621);Loss of phosphorylation at S299 (P = 0.0621);
MVP		0.16
MPC		0.22
ClinPred		0.76	D
GERP RS		4.8
Varity_R		0.093
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs1773323843; hg19: chr6-105563624;