chrX-153700945-C-T

Variant names:

• chrX-153700945-C-T
• NM_001256447.2:c.733G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256447.2(BCAP31):​c.733G>A​(p.Glu245Lys) variant causes a missense 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. 12/19 in silico tools predict a benign 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
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.446

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13789475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAP31	NM_001256447.2	c.733G>A	p.Glu245Lys	missense_variant	Exon 8 of 8	ENST00000345046.12	NP_001243376.1
BCAP31	NM_001139457.2	c.934G>A	p.Glu312Lys	missense_variant	Exon 8 of 8		NP_001132929.1
BCAP31	NM_001139441.1	c.733G>A	p.Glu245Lys	missense_variant	Exon 8 of 8		NP_001132913.1
BCAP31	NM_005745.8	c.733G>A	p.Glu245Lys	missense_variant	Exon 8 of 8		NP_005736.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAP31	ENST00000345046.12	c.733G>A	p.Glu245Lys	missense_variant	Exon 8 of 8	1	NM_001256447.2	ENSP00000343458.6

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.934G>A (p.E312K) alteration is located in exon 8 (coding exon 8) of the BCAP31 gene. This alteration results from a G to A substitution at nucleotide position 934, causing the glutamic acid (E) at amino acid position 312 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1

Jan 12, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	.;T;T;.
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.46	T;.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.6	.;L;L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.0	N;N;.;.
REVEL	Benign	0.048
Sift	Benign	0.086	T;T;.;.
Sift4G	Benign	0.17	T;T;.;.
Polyphen		0.0080	.;B;B;.
Vest4		0.21
MutPred		0.12		.;Gain of ubiquitination at E245 (P = 0.0247);Gain of ubiquitination at E245 (P = 0.0247);.;
MVP		0.75
MPC		0.87
ClinPred		0.55	D
GERP RS		3.9
Varity_R		0.20
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152966400;