3-133807800-G-A

Position:

• chr3-133807800-G-A

Variant summary

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

The NM_001379313.1(SRPRB):​c.304G>A​(p.Val102Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: SRPRB NM_001379313.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0340

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]

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=0.077023566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPRB	NM_001379313.1	c.304G>A	p.Val102Ile	missense_variant	3/7	ENST00000678299.1	NP_001366242.1
SRPRB	NM_021203.4	c.304G>A	p.Val102Ile	missense_variant	4/8		NP_067026.3
SRPRB	NR_163491.1	n.338G>A		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPRB	ENST00000678299.1	c.304G>A	p.Val102Ile	missense_variant	3/7		NM_001379313.1	ENSP00000503923	P1
SRPRB	ENST00000466490.7	c.304G>A	p.Val102Ile	missense_variant	4/8	5		ENSP00000418401	P1
SRPRB	ENST00000494297.5	n.206G>A		non_coding_transcript_exon_variant	2/6	2
SRPRB	ENST00000484684.1			downstream_gene_variant		2		ENSP00000417096

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

May 15, 2024

The c.304G>A (p.V102I) 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 304, causing the valine (V) at amino acid position 102 to be replaced by an isoleucine (I). 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	0.073
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.72
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.72	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.035
Sift	Benign	0.43	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.46		Loss of sheet (P = 0.0357);
MVP		0.10
MPC		0.17
ClinPred		0.051	T
GERP RS		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.013
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-133526644;