6-105115799-C-T

Variant names:

• chr6-105115799-C-T
• NM_001199563.2:c.845G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001199563.2(BVES):​c.845G>A​(p.Ser282Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,562 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 5.92

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BVES	NM_001199563.2	c.845G>A	p.Ser282Asn	missense_variant	Exon 7 of 8	ENST00000314641.10	NP_001186492.1
BVES	NM_007073.4	c.845G>A	p.Ser282Asn	missense_variant	Exon 7 of 8		NP_009004.2
BVES	NM_147147.4	c.845G>A	p.Ser282Asn	missense_variant	Exon 7 of 8		NP_671488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BVES	ENST00000314641.10	c.845G>A	p.Ser282Asn	missense_variant	Exon 7 of 8	1	NM_001199563.2	ENSP00000313172.5
BVES	ENST00000336775.9	c.845G>A	p.Ser282Asn	missense_variant	Exon 7 of 8	1		ENSP00000337259.5
BVES	ENST00000446408.2	c.845G>A	p.Ser282Asn	missense_variant	Exon 7 of 8	1		ENSP00000397310.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461562 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727102

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

BVES-related disorder Uncertain:1

Oct 10, 2023

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The BVES c.845G>A variant is predicted to result in the amino acid substitution p.Ser282Asn. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.72	.;.;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.023	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.88
MutPred		0.24		Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);
MVP		0.40
MPC		0.83
ClinPred		0.97	D
GERP RS		6.0
Varity_R		0.30
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr6-105563674;