X-153720968-G-A

Variant names:

• chrX-153720968-G-A
• rs397515620
• NM_001256447.2:c.97C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001256447.2(BCAP31):​c.97C>T​(p.Gln33*) variant causes a stop gained change. 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: BCAP31 NM_001256447.2 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.07
• Publications: 3 publications found

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]

BCAP31 Gene-Disease associations (from GenCC):

• severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome

  Inheritance: XL, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-153720968-G-A is Pathogenic according to our data. Variant chrX-153720968-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 68446.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256447.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAP31	NM_001256447.2	MANE Select	c.97C>T	p.Gln33*	stop_gained	Exon 3 of 8	NP_001243376.1
	BCAP31	NM_001139457.2		c.298C>T	p.Gln100*	stop_gained	Exon 3 of 8	NP_001132929.1
	BCAP31	NM_001139441.1		c.97C>T	p.Gln33*	stop_gained	Exon 3 of 8	NP_001132913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAP31	ENST00000345046.12	TSL:1 MANE Select	c.97C>T	p.Gln33*	stop_gained	Exon 3 of 8	ENSP00000343458.6
	BCAP31	ENST00000458587.8	TSL:1	c.298C>T	p.Gln100*	stop_gained	Exon 3 of 8	ENSP00000392330.2
	BCAP31	ENST00000647529.1		c.97C>T	p.Gln33*	stop_gained	Exon 4 of 9	ENSP00000494052.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Sep 05, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	37
DANN	Uncertain	1.0
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		6.1
Vest4		0.86
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/200	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs397515620; hg19: chrX-152986423;