Variant 9-113349608-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017688.3(BSPRY):c.29C>T(p.Pro10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000865 in 1,040,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

BSPRY
NM_017688.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.14

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.110015124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BSPRY	NM_017688.3 linkuse as main transcript	c.29C>T	p.Pro10Leu	missense_variant	1/6	ENST00000374183.5
BSPRY	NM_001317943.2 linkuse as main transcript	c.29C>T	p.Pro10Leu	missense_variant	1/6
BSPRY	NM_001317944.2 linkuse as main transcript	c.29C>T	p.Pro10Leu	missense_variant	1/5
BSPRY	XM_006717149.4 linkuse as main transcript	c.29C>T	p.Pro10Leu	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSPRY	ENST00000374183.5 linkuse as main transcript	c.29C>T	p.Pro10Leu	missense_variant	1/6	1	NM_017688.3	P1	Q5W0U4-1
BSPRY	ENST00000462085.1 linkuse as main transcript	n.67C>T		non_coding_transcript_exon_variant	1/5	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000865

AC:

AN:

1040248

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

492348

show subpopulations

Gnomad4 AFR exome

AF:

0.0000473

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000135

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000559

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000627

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

Dec 11, 2023

The c.29C>T (p.P10L) alteration is located in exon 1 (coding exon 1) of the BSPRY gene. This alteration results from a C to T substitution at nucleotide position 29, causing the proline (P) at amino acid position 10 to be replaced by a leucine (L). 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

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.5

DANN

Benign

0.97

DEOGEN2

Benign

0.0035

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.81

REVEL

Benign

0.029

Sift

Uncertain

0.010

Sift4G

Uncertain

0.059

Polyphen

0.0

Vest4

0.17

MutPred

0.38

Gain of catalytic residue at P10 (P = 0.0115);

MVP

0.28

MPC

0.070

ClinPred

0.12

GERP RS

0.24

Varity_R

0.062

gMVP

0.26

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