X-153700939-A-G

Position:

• chrX-153700939-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_001256447.2(BCAP31):​c.739T>C​(p.Ter247GlnextTer89) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: BCAP31 NM_001256447.2 stop_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.86

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001256447.2 Downstream stopcodon found after 12 codons.
• PP5: Variant X-153700939-A-G is Pathogenic according to our data. Variant chrX-153700939-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 522085.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAP31	NM_001256447.2	c.739T>C	p.Ter247GlnextTer89	stop_lost	8/8	ENST00000345046.12	NP_001243376.1
BCAP31	NM_001139457.2	c.940T>C	p.Ter314GlnextTer89	stop_lost	8/8		NP_001132929.1
BCAP31	NM_001139441.1	c.739T>C	p.Ter247GlnextTer89	stop_lost	8/8		NP_001132913.1
BCAP31	NM_005745.8	c.739T>C	p.Ter247GlnextTer89	stop_lost	8/8		NP_005736.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAP31	ENST00000345046.12	c.739T>C	p.Ter247GlnextTer89	stop_lost	8/8	1	NM_001256447.2	ENSP00000343458	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.85
FATHMM_MKL	Benign	0.55	D
MutationTaster	Benign	1.0	N;N;N
Vest4		0.098
GERP RS		3.9

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

Other links and lift over

dbSNP: rs1557047215; hg19: chrX-152966394;