Variant 3-133805967-T-C 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_001379313.1(SRPRB):c.119T>C(p.Val40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,461,082 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: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SRPRB
NM_001379313.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

SRPRB (HGNC:24085): (SRP receptor subunit beta) The protein encoded by this gene has similarity to mouse protein which is a subunit of the signal recognition particle receptor (SR). This subunit is a transmembrane GTPase belonging to the GTPase superfamily. It anchors alpha subunit, a peripheral membrane GTPase, to the ER membrane. SR is required for the cotranslational targeting of both secretory and membrane proteins to the ER membrane. [provided by RefSeq, Jul 2008]

SRPRB links:

ENSG00000285908 (HGNC:):

ENSG00000285908 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=0.17808545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPRB	NM_001379313.1 linkuse as main transcript	c.119T>C	p.Val40Ala	missense_variant	1/7	ENST00000678299.1	NP_001366242.1
SRPRB	NM_021203.4 linkuse as main transcript	c.119T>C	p.Val40Ala	missense_variant	2/8		NP_067026.3	Q9Y5M8Q549N5
SRPRB	NR_163491.1 linkuse as main transcript	n.153T>C		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRPRB	ENST00000678299.1 linkuse as main transcript	c.119T>C	p.Val40Ala	missense_variant	1/7		NM_001379313.1	ENSP00000503923.1	Q9Y5M8
SRPRB	ENST00000466490.7 linkuse as main transcript	c.119T>C	p.Val40Ala	missense_variant	2/8	5		ENSP00000418401.1	Q9Y5M8
SRPRB	ENST00000484684.1 linkuse as main transcript	c.119T>C	p.Val40Ala	missense_variant	1/3	2		ENSP00000417096.1	C9J5Z8
ENSG00000285908	ENST00000650377.1 linkuse as main transcript	n.173A>G		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249808

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461082

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000297

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jul 12, 2022

The c.119T>C (p.V40A) alteration is located in exon 2 (coding exon 1) of the SRPRB gene. This alteration results from a T to C substitution at nucleotide position 119, causing the valine (V) at amino acid position 40 to be replaced by an alanine (A). 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

0.12

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.15

Sift

Benign

0.079

T;T

Sift4G

Uncertain

0.050

T;T

Polyphen

0.0010

B;.

Vest4

0.15

MutPred

0.27

Loss of glycosylation at P35 (P = 0.0606);Loss of glycosylation at P35 (P = 0.0606);

MVP

0.65

MPC

0.26

ClinPred

0.36

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.15

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