3-133805898-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001379313.1(SRPRB):c.50G>T(p.Gly17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,240 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: 0.0000041 (0 hom.)
• Consequence: SRPRB NM_001379313.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11

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]

(HGNC:):

ACMG classification

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=0.1790894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRPRB	NM_001379313.1	c.50G>T	p.Gly17Val	missense_variant	1/7	ENST00000678299.1
SRPRB	NM_021203.4	c.50G>T	p.Gly17Val	missense_variant	2/8
SRPRB	NR_163491.1	n.84G>T		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRPRB	ENST00000678299.1	c.50G>T	p.Gly17Val	missense_variant	1/7		NM_001379313.1	P1
	ENST00000650377.1	n.242C>A		non_coding_transcript_exon_variant	1/2
SRPRB	ENST00000466490.7	c.50G>T	p.Gly17Val	missense_variant	2/8	5		P1
SRPRB	ENST00000484684.1	c.50G>T	p.Gly17Val	missense_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461240 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726970

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.50G>T (p.G17V) alteration is located in exon 2 (coding exon 1) of the SRPRB gene. This alteration results from a G to T substitution at nucleotide position 50, causing the glycine (G) at amino acid position 17 to be replaced by a valine (V). 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	0.096
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	21
Dann	Benign	0.94
DEOGEN2	Benign	0.0085	T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.0010	B;.
Vest4		0.44
MVP		0.70
MPC		0.36
ClinPred		0.42	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.094
gMVP		0.56

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

Other links and lift over

dbSNP: rs747654946; hg19: chr3-133524742;