11-126265037-C-T

Variant names:

• chr11-126265037-C-T
• NM_003139.4:c.1447G>A

Variant summary

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

The NM_003139.4(SRPRA):​c.1447G>A​(p.Gly483Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SRPRA NM_003139.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.54

Genes affected

SRPRA (HGNC:11307): (SRP receptor subunit alpha) The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPRA	NM_003139.4	c.1447G>A	p.Gly483Ser	missense_variant	Exon 11 of 14	ENST00000332118.11	NP_003130.2
SRPRA	NM_001177842.2	c.1363G>A	p.Gly455Ser	missense_variant	Exon 10 of 13		NP_001171313.1
SRPRA	XM_047427497.1	c.1447G>A	p.Gly483Ser	missense_variant	Exon 11 of 14		XP_047283453.1
SRPRA	XM_017018179.3	c.1447G>A	p.Gly483Ser	missense_variant	Exon 11 of 14		XP_016873668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPRA	ENST00000332118.11	c.1447G>A	p.Gly483Ser	missense_variant	Exon 11 of 14	1	NM_003139.4	ENSP00000328023.5
SRPRA	ENST00000532259.1	c.1363G>A	p.Gly455Ser	missense_variant	Exon 10 of 13	2		ENSP00000435508.1
SRPRA	ENST00000531104.1	n.526G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
SRPRA	ENST00000527817.1	n.*43G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

SRPRA-related disorder Uncertain:1

Sep 26, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The SRPRA c.1447G>A variant is predicted to result in the amino acid substitution p.Gly483Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.69	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.25
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.89	P;.
Vest4		0.78
MutPred		0.23		Loss of sheet (P = 0.0457);.;
MVP		0.59
MPC		1.1
ClinPred		0.97	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.61
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr11-126134932;