Variant chr9-113349724-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017688.3(BSPRY):c.145G>C(p.Gly49Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000179 in 1,239,664 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

BSPRY
NM_017688.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSPRY	NM_017688.3 linkuse as main transcript	c.145G>C	p.Gly49Arg	missense_variant	1/6	ENST00000374183.5	NP_060158.2	Q5W0U4-1
BSPRY	NM_001317943.2 linkuse as main transcript	c.145G>C	p.Gly49Arg	missense_variant	1/6		NP_001304872.1	Q5W0U4
BSPRY	NM_001317944.2 linkuse as main transcript	c.145G>C	p.Gly49Arg	missense_variant	1/5		NP_001304873.1	Q5W0U4-2
BSPRY	XM_006717149.4 linkuse as main transcript	c.145G>C	p.Gly49Arg	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.145G>C	p.Gly49Arg	missense_variant	1/6	1	NM_017688.3	ENSP00000363298.4		Q5W0U4-1
BSPRY	ENST00000462085.1 linkuse as main transcript	n.183G>C		non_coding_transcript_exon_variant	1/5	1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000199

AC:

216

AN:

1087816

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

109

AN XY:

518940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000229

Gnomad4 OTH exome

AF:

0.0000926

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151848

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

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

May 05, 2023

The c.145G>C (p.G49R) alteration is located in exon 1 (coding exon 1) of the BSPRY gene. This alteration results from a G to C substitution at nucleotide position 145, causing the glycine (G) at amino acid position 49 to be replaced by an arginine (R). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

0.066

Eigen_PC

Benign

0.0092

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.48

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.4

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.32

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.30

MutPred

0.52

Gain of MoRF binding (P = 0.0362);

MVP

0.68

MPC

0.45

ClinPred

0.95

GERP RS

3.4

Varity_R

0.35

gMVP

0.45

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