chrX-153700969-C-G

Variant names:

• chrX-153700969-C-G
• NM_001256447.2:c.709G>C

Variant summary

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

The NM_001256447.2(BCAP31):​c.709G>C​(p.Val237Leu) 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. 14/19 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)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: BCAP31 NM_001256447.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.658

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=0.08142239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAP31	NM_001256447.2	c.709G>C	p.Val237Leu	missense_variant	Exon 8 of 8	ENST00000345046.12	NP_001243376.1
BCAP31	NM_001139457.2	c.910G>C	p.Val304Leu	missense_variant	Exon 8 of 8		NP_001132929.1
BCAP31	NM_001139441.1	c.709G>C	p.Val237Leu	missense_variant	Exon 8 of 8		NP_001132913.1
BCAP31	NM_005745.8	c.709G>C	p.Val237Leu	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.709G>C	p.Val237Leu	missense_variant	Exon 8 of 8	1	NM_001256447.2	ENSP00000343458.6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1093913 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 360079

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome Uncertain:1

Jul 28, 2020

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.7
DANN	Benign	0.77
DEOGEN2	Benign	0.063	.;T;T;.
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.66	T;.;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.081	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.35	N;N;.;.
REVEL	Benign	0.036
Sift	Benign	0.29	T;T;.;.
Sift4G	Benign	0.96	T;T;.;.
Polyphen		0.0050	.;B;B;.
Vest4		0.12
MutPred		0.26		.;Loss of catalytic residue at V237 (P = 0.0452);Loss of catalytic residue at V237 (P = 0.0452);.;
MVP		0.19
MPC		0.74
ClinPred		0.029	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.090
gMVP		0.095

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152966424;