rs782683945

Variant names:

• chrX-153703019-C-A
• rs782683945
• NM_001256447.2:c.517G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_001256447.2(BCAP31):​c.517G>T​(p.Ala173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,096,385 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000082 (0 hom. 1 hem.)
• Consequence: BCAP31 NM_001256447.2 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -1.43
• Publications: 1 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043188393).
• BP6: Variant X-153703019-C-A is Benign according to our data. Variant chrX-153703019-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 599439.

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.517G>T	p.Ala173Ser	missense	Exon 6 of 8	NP_001243376.1	P51572-1
	BCAP31	NM_001139457.2		c.718G>T	p.Ala240Ser	missense	Exon 6 of 8	NP_001132929.1	P51572-2
	BCAP31	NM_001139441.1		c.517G>T	p.Ala173Ser	missense	Exon 6 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.517G>T	p.Ala173Ser	missense	Exon 6 of 8	ENSP00000343458.6	P51572-1
	BCAP31	ENST00000458587.8	TSL:1	c.718G>T	p.Ala240Ser	missense	Exon 6 of 8	ENSP00000392330.2	P51572-2
	BCAP31	ENST00000928875.1		c.598G>T	p.Ala200Ser	missense	Exon 7 of 9	ENSP00000598934.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.0000383 AC: 7 AN: 182741 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000255

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 9 AN: 1096385 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362741

African (AFR) AF: 0.00 AC: 0 AN: 26350

American (AMR) AF: 0.000256 AC: 9 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3060

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841935

Other (OTH) AF: 0.00 AC: 0 AN: 45966

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.043
DANN	Benign	0.68
DEOGEN2	Benign	0.073	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.94	L
PhyloP100		-1.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.0080
Sift	Benign	0.28	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.047
MutPred		0.33		Gain of phosphorylation at A173 (P = 0.0283)
MVP		0.42
MPC		0.68
ClinPred		0.0090	T
GERP RS		-1.1
Varity_R		0.13
gMVP		0.12
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

dbSNP: rs782683945; hg19: chrX-152968474;