chrX-153700975-C-T

Position:

• chrX-153700975-C-T

Variant summary

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

The NM_001256447.2(BCAP31):​c.703G>A​(p.Ala235Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A235V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: BCAP31 NM_001256447.2 missense, splice_region
• Scores: Splicing: ADA: 0.004603
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.617

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]

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=0.03117901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAP31	NM_001256447.2	c.703G>A	p.Ala235Thr	missense_variant, splice_region_variant	8/8	ENST00000345046.12
BCAP31	NM_001139457.2	c.904G>A	p.Ala302Thr	missense_variant, splice_region_variant	8/8
BCAP31	NM_001139441.1	c.703G>A	p.Ala235Thr	missense_variant, splice_region_variant	8/8
BCAP31	NM_005745.8	c.703G>A	p.Ala235Thr	missense_variant, splice_region_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAP31	ENST00000345046.12	c.703G>A	p.Ala235Thr	missense_variant, splice_region_variant	8/8	1	NM_001256447.2	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

BCAP31-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 22, 2023

The BCAP31 c.703G>A variant is predicted to result in the amino acid substitution p.Ala235Thr. To our knowledge, this variant has not been reported in the literature or in a large population database, 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	0.085
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.92
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.76	T;.;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.031	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.15	N;N;.;.
REVEL	Benign	0.025
Sift	Benign	0.17	T;T;.;.
Sift4G	Benign	0.43	T;T;.;.
Polyphen		0.38	.;B;B;.
Vest4		0.22
MutPred		0.15		.;Gain of phosphorylation at A235 (P = 0.0588);Gain of phosphorylation at A235 (P = 0.0588);.;
MVP		0.49
MPC		0.92
ClinPred		0.16	T
GERP RS		3.5
Varity_R		0.070
gMVP		0.065

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0046
dbscSNV1_RF	Benign	0.16
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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152966430;