Variant chr3-133807795-G-A 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.299G>A(p.Cys100Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,530 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SRPRB
NM_001379313.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

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:

SRPRB (HGNC:):

SRPRB 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=0.24162343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPRB	NM_001379313.1 linkuse as main transcript	c.299G>A	p.Cys100Tyr	missense_variant	3/7	ENST00000678299.1	NP_001366242.1
SRPRB	NM_021203.4 linkuse as main transcript	c.299G>A	p.Cys100Tyr	missense_variant	4/8		NP_067026.3	Q9Y5M8Q549N5
SRPRB	NR_163491.1 linkuse as main transcript	n.333G>A		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRPRB	ENST00000678299.1 linkuse as main transcript	c.299G>A	p.Cys100Tyr	missense_variant	3/7		NM_001379313.1	ENSP00000503923.1	Q9Y5M8
SRPRB	ENST00000466490.7 linkuse as main transcript	c.299G>A	p.Cys100Tyr	missense_variant	4/8	5		ENSP00000418401.1	Q9Y5M8
SRPRB	ENST00000494297.5 linkuse as main transcript	n.201G>A		non_coding_transcript_exon_variant	2/6	2
SRPRB	ENST00000484684.1 linkuse as main transcript	c.*21G>A		downstream_gene_variant		2		ENSP00000417096.1	C9J5Z8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152124

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460406

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726496

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

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

Jan 30, 2024

The c.299G>A (p.C100Y) alteration is located in exon 4 (coding exon 3) of the SRPRB gene. This alteration results from a G to A substitution at nucleotide position 299, causing the cysteine (C) at amino acid position 100 to be replaced by a tyrosine (Y). 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

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

M_CAP

Benign

0.0072

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.77

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.62

REVEL

Benign

0.10

Sift

Benign

0.10

Sift4G

Benign

0.12

Polyphen

0.017

Vest4

0.31

MutPred

0.72

Gain of disorder (P = 0.0581);

MVP

0.27

MPC

0.36

ClinPred

0.33

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.093

gMVP

0.58

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