NM_001256447.2:c.722T>C

Variant names:

• chrX-153700956-A-G
• NM_001256447.2:c.722T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001256447.2(BCAP31):​c.722T>C​(p.Met241Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,094,293 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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: 9.1e-7 (0 hom. 0 hem.)
• Consequence: BCAP31 NM_001256447.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.732
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02858296).

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.722T>C	p.Met241Thr	missense	Exon 8 of 8	NP_001243376.1	P51572-1
	BCAP31	NM_001139457.2		c.923T>C	p.Met308Thr	missense	Exon 8 of 8	NP_001132929.1	P51572-2
	BCAP31	NM_001139441.1		c.722T>C	p.Met241Thr	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.722T>C	p.Met241Thr	missense	Exon 8 of 8	ENSP00000343458.6	P51572-1
	BCAP31	ENST00000458587.8	TSL:1	c.923T>C	p.Met308Thr	missense	Exon 8 of 8	ENSP00000392330.2	P51572-2
	BCAP31	ENST00000928875.1		c.803T>C	p.Met268Thr	missense	Exon 9 of 9	ENSP00000598934.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1094293 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 360381

African (AFR) AF: 0.0000381 AC: 1 AN: 26226

American (AMR) AF: 0.00 AC: 0 AN: 34743

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19290

East Asian (EAS) AF: 0.00 AC: 0 AN: 29790

South Asian (SAS) AF: 0.00 AC: 0 AN: 53409

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40497

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4065

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840339

Other (OTH) AF: 0.00 AC: 0 AN: 45934

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.038
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.62
DEOGEN2	Benign	0.064	T
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.035	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		0.73
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.10
Sift	Benign	0.70	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.092
MutPred		0.15		Gain of phosphorylation at M241 (P = 0.0065)
MVP		0.11
MPC		0.84
ClinPred		0.024	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.050
Mutation Taster		=93/7	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

hg19: chrX-152966411;