rs1057518852

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001256447.2(BCAP31):​c.119T>C​(p.Leu40Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 23)

Consequence

BCAP31
NM_001256447.2 missense

Scores

7
7
3

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 8.03
Variant links:
Genes affected
BCAP31 (HGNC:16695): (B cell receptor associated protein 31) This gene encodes a member of the B-cell receptor associated protein 31 superfamily. The encoded protein is a multi-pass transmembrane protein of the endoplasmic reticulum that is involved in the anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi and in caspase 8-mediated apoptosis. Microdeletions in this gene are associated with contiguous ABCD1/DXS1375E deletion syndrome (CADDS), a neonatal disorder. Alternative splicing of this gene results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 16. [provided by RefSeq, Jan 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BCAP31NM_001256447.2 linkc.119T>C p.Leu40Pro missense_variant 3/8 ENST00000345046.12 NP_001243376.1 P51572-1
BCAP31NM_001139457.2 linkc.320T>C p.Leu107Pro missense_variant 3/8 NP_001132929.1 P51572-2
BCAP31NM_001139441.1 linkc.119T>C p.Leu40Pro missense_variant 3/8 NP_001132913.1 P51572-1
BCAP31NM_005745.8 linkc.119T>C p.Leu40Pro missense_variant 3/8 NP_005736.3 P51572-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BCAP31ENST00000345046.12 linkc.119T>C p.Leu40Pro missense_variant 3/81 NM_001256447.2 ENSP00000343458.6 P51572-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Seizure;C0557874:Global developmental delay Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaJan 27, 2015- -
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 06, 2022The c.320T>C (p.L107P) alteration is located in exon 3 (coding exon 3) of the BCAP31 gene. This alteration results from a T to C substitution at nucleotide position 320, causing the leucine (L) at amino acid position 107 to be replaced by a proline (P). 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
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.56
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.52
.;D;D;.;T;.;T;.;T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T;.;T;T;D;D;D;D;T
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.96
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Uncertain
2.1
.;M;M;.;.;.;.;.;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-5.0
D;D;.;.;D;D;D;D;D
REVEL
Pathogenic
0.79
Sift
Uncertain
0.0020
D;D;.;.;D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;.;.;.;D;D;.;.
Polyphen
1.0
.;D;D;.;.;.;.;.;.
Vest4
0.77
MutPred
0.81
.;Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP
0.96
MPC
2.3
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.96
gMVP
0.97

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

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

Other links and lift over

dbSNP: rs1057518852; hg19: chrX-152986401; API