Variant 9-113349710-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_017688.3(BSPRY):c.131G>T(p.Cys44Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000404 in 1,238,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Consequence

BSPRY
NM_017688.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66

Variant links:

Genes affected

BSPRY (HGNC:18232): (B-box and SPRY domain containing) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in cell leading edge; membrane; and perinuclear region of cytoplasm. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BSPRY links:

BSPRY (HGNC:):

BSPRY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSPRY	NM_017688.3 linkuse as main transcript	c.131G>T	p.Cys44Phe	missense_variant	1/6	ENST00000374183.5	NP_060158.2	Q5W0U4-1
BSPRY	NM_001317943.2 linkuse as main transcript	c.131G>T	p.Cys44Phe	missense_variant	1/6		NP_001304872.1	Q5W0U4
BSPRY	NM_001317944.2 linkuse as main transcript	c.131G>T	p.Cys44Phe	missense_variant	1/5		NP_001304873.1	Q5W0U4-2
BSPRY	XM_006717149.4 linkuse as main transcript	c.131G>T	p.Cys44Phe	missense_variant	1/6		XP_006717212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSPRY	ENST00000374183.5 linkuse as main transcript	c.131G>T	p.Cys44Phe	missense_variant	1/6	1	NM_017688.3	ENSP00000363298.4		Q5W0U4-1
BSPRY	ENST00000462085.1 linkuse as main transcript	n.169G>T		non_coding_transcript_exon_variant	1/5	1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.20e-7

AC:

AN:

1086924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

518546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000397

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151842

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000181

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.131G>T (p.C44F) alteration is located in exon 1 (coding exon 1) of the BSPRY gene. This alteration results from a G to T substitution at nucleotide position 131, causing the cysteine (C) at amino acid position 44 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.86

MetaRNN

Pathogenic

0.98

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.8

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-7.4

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.79

MutPred

0.90

Gain of MoRF binding (P = 0.0688);

MVP

0.93

MPC

0.50

ClinPred

1.0

GERP RS

3.4

Varity_R

0.95

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over