rs1557047235

Variant names:

• chrX-153700962-C-T
• rs1557047235
• NM_001256447.2:c.716G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001256447.2(BCAP31):​c.716G>A​(p.Gly239Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000913 in 1,205,017 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000091 (0 hom. 3 hem.)
• Consequence: BCAP31 NM_001256447.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:4
• Conservation: PhyloP100: 1.56
• Publications: 0 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: AR, XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.117408276).
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAP31	NM_001256447.2	MANE Select	c.716G>A	p.Gly239Asp	missense	Exon 8 of 8	NP_001243376.1	P51572-1
	BCAP31	NM_001139457.2		c.917G>A	p.Gly306Asp	missense	Exon 8 of 8	NP_001132929.1	P51572-2
	BCAP31	NM_001139441.1		c.716G>A	p.Gly239Asp	missense	Exon 8 of 8	NP_001132913.1	P51572-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAP31	ENST00000345046.12	TSL:1 MANE Select	c.716G>A	p.Gly239Asp	missense	Exon 8 of 8	ENSP00000343458.6	P51572-1
	BCAP31	ENST00000458587.8	TSL:1	c.917G>A	p.Gly306Asp	missense	Exon 8 of 8	ENSP00000392330.2	P51572-2
	BCAP31	ENST00000928875.1		c.797G>A	p.Gly266Asp	missense	Exon 9 of 9	ENSP00000598934.1

Frequencies

GnomAD3 genomes AF: 0.00000898 AC: 1 AN: 111369 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000574 AC: 1 AN: 174163 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000914 AC: 10 AN: 1093648 Hom.: 0 Cov.: 30 AF XY: 0.00000834 AC XY: 3 AN XY: 359838

African (AFR) AF: 0.00 AC: 0 AN: 26202

American (AMR) AF: 0.00 AC: 0 AN: 34667

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19271

East Asian (EAS) AF: 0.00 AC: 0 AN: 29706

South Asian (SAS) AF: 0.00 AC: 0 AN: 53261

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40491

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4083

European-Non Finnish (NFE) AF: 0.0000107 AC: 9 AN: 840069

Other (OTH) AF: 0.0000218 AC: 1 AN: 45898

GnomAD4 genome AF: 0.00000898 AC: 1 AN: 111369 Hom.: 0 Cov.: 23 AF XY: 0.0000298 AC XY: 1 AN XY: 33581

African (AFR) AF: 0.00 AC: 0 AN: 30600

American (AMR) AF: 0.00 AC: 0 AN: 10590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2639

East Asian (EAS) AF: 0.00 AC: 0 AN: 3503

South Asian (SAS) AF: 0.00 AC: 0 AN: 2650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52980

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	2	-	Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.6
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.18
Sift	Benign	0.068	T
Sift4G	Benign	0.12	T
Polyphen		0.66	P
Vest4		0.33
MutPred		0.16		Gain of methylation at K243 (P = 0.1162)
MVP		0.59
MPC		1.0
ClinPred		0.22	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.10
Mutation Taster		=81/19	polymorphism

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: rs1557047235; hg19: chrX-152966417;