rs869025337

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong

The NM_001199563.2(BVES):​c.602C>T​(p.Ser201Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

BVES
NM_001199563.2 missense

Scores

13
3
3

Clinical Significance

Likely pathogenic criteria provided, multiple submitters, no conflicts P:3

Conservation

PhyloP100: 9.92
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.918
PP5
Variant 6-105124593-G-A is Pathogenic according to our data. Variant chr6-105124593-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 222033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-105124593-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BVESNM_001199563.2 linkuse as main transcriptc.602C>T p.Ser201Phe missense_variant 5/8 ENST00000314641.10 NP_001186492.1 Q8NE79
BVESNM_007073.4 linkuse as main transcriptc.602C>T p.Ser201Phe missense_variant 5/8 NP_009004.2 Q8NE79
BVESNM_147147.4 linkuse as main transcriptc.602C>T p.Ser201Phe missense_variant 5/8 NP_671488.1 Q8NE79

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BVESENST00000314641.10 linkuse as main transcriptc.602C>T p.Ser201Phe missense_variant 5/81 NM_001199563.2 ENSP00000313172.5 Q8NE79
BVESENST00000336775.9 linkuse as main transcriptc.602C>T p.Ser201Phe missense_variant 5/81 ENSP00000337259.5 Q8NE79
BVESENST00000446408.2 linkuse as main transcriptc.602C>T p.Ser201Phe missense_variant 5/81 ENSP00000397310.2 Q8NE79

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460688
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726742
show subpopulations
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2X Pathogenic:2
Likely pathogenic, criteria provided, single submitterclinical testingRevvity Omics, RevvityAug 05, 2019- -
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 22, 2019- -
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingGeneDxJan 08, 2024Published functional studies demonstrate a damaging effect (PMID: 26642364, 36624536); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27347491, 28939104, 31197601, 29534001, 36254885, 26642364, 36624536, 36155908) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.20
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.38
T;T;T
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.98
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
.;.;D
M_CAP
Uncertain
0.098
D
MetaRNN
Pathogenic
0.92
D;D;D
MetaSVM
Benign
-0.42
T
MutationAssessor
Pathogenic
2.9
M;M;M
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.6
D;D;D
REVEL
Pathogenic
0.76
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.97
MutPred
0.74
Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);
MVP
0.84
MPC
0.92
ClinPred
1.0
D
GERP RS
5.9
Varity_R
0.88
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs869025337; hg19: chr6-105572468; COSMIC: COSV58947039; API