rs869025337
Positions:
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
NM_001199563.2 missense
Scores
13
3
3
Clinical Significance
Conservation
PhyloP100: 9.92
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]
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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 |
---|---|---|---|---|---|---|---|---|
BVES | NM_001199563.2 | c.602C>T | p.Ser201Phe | missense_variant | 5/8 | ENST00000314641.10 | NP_001186492.1 | |
BVES | NM_007073.4 | c.602C>T | p.Ser201Phe | missense_variant | 5/8 | NP_009004.2 | ||
BVES | NM_147147.4 | c.602C>T | p.Ser201Phe | missense_variant | 5/8 | NP_671488.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BVES | ENST00000314641.10 | c.602C>T | p.Ser201Phe | missense_variant | 5/8 | 1 | NM_001199563.2 | ENSP00000313172.5 | ||
BVES | ENST00000336775.9 | c.602C>T | p.Ser201Phe | missense_variant | 5/8 | 1 | ENSP00000337259.5 | |||
BVES | ENST00000446408.2 | c.602C>T | p.Ser201Phe | missense_variant | 5/8 | 1 | ENSP00000397310.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460688Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726742
GnomAD4 exome
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AC:
4
AN:
1460688
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Cov.:
30
AF XY:
AC XY:
2
AN XY:
726742
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
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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 submitter | clinical testing | Revvity Omics, Revvity | Aug 05, 2019 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 22, 2019 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2024 | Published 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at