Variant 3-133806671-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001379313.1(SRPRB):c.217T>G(p.Cys73Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SRPRB
NM_001379313.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.51

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SRPRB	NM_001379313.1 linkuse as main transcript	c.217T>G	p.Cys73Gly	missense_variant	2/7	ENST00000678299.1	NP_001366242.1
SRPRB	NM_021203.4 linkuse as main transcript	c.217T>G	p.Cys73Gly	missense_variant	3/8		NP_067026.3
SRPRB	NR_163491.1 linkuse as main transcript	n.251T>G		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SRPRB	ENST00000678299.1 linkuse as main transcript	c.217T>G	p.Cys73Gly	missense_variant	2/7		NM_001379313.1	ENSP00000503923	P1
SRPRB	ENST00000466490.7 linkuse as main transcript	c.217T>G	p.Cys73Gly	missense_variant	3/8	5		ENSP00000418401	P1
SRPRB	ENST00000484684.1 linkuse as main transcript	c.217T>G	p.Cys73Gly	missense_variant	2/3	2		ENSP00000417096
SRPRB	ENST00000494297.5 linkuse as main transcript	n.119T>G		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251486

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135916

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727222

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

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

Apr 23, 2024

The c.217T>G (p.C73G) alteration is located in exon 3 (coding exon 2) of the SRPRB gene. This alteration results from a T to G substitution at nucleotide position 217, causing the cysteine (C) at amino acid position 73 to be replaced by a glycine (G). 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

0.38

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

T;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

T;D

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-8.6

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.99

D;.

Vest4

0.81

MutPred

0.64

Loss of stability (P = 0.0337);Loss of stability (P = 0.0337);

MVP

0.87

MPC

0.88

ClinPred

0.99

GERP RS

5.3

Varity_R

0.73

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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