11-126265132-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_003139.4(SRPRA):ā€‹c.1352T>Cā€‹(p.Ile451Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,106 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

SRPRA
NM_003139.4 missense

Scores

11
5
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.82
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.855
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRPRANM_003139.4 linkc.1352T>C p.Ile451Thr missense_variant Exon 11 of 14 ENST00000332118.11 NP_003130.2 P08240-1
SRPRANM_001177842.2 linkc.1268T>C p.Ile423Thr missense_variant Exon 10 of 13 NP_001171313.1 P08240-2
SRPRAXM_047427497.1 linkc.1352T>C p.Ile451Thr missense_variant Exon 11 of 14 XP_047283453.1
SRPRAXM_017018179.3 linkc.1352T>C p.Ile451Thr missense_variant Exon 11 of 14 XP_016873668.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRPRAENST00000332118.11 linkc.1352T>C p.Ile451Thr missense_variant Exon 11 of 14 1 NM_003139.4 ENSP00000328023.5 P08240-1
SRPRAENST00000532259.1 linkc.1268T>C p.Ile423Thr missense_variant Exon 10 of 13 2 ENSP00000435508.1 P08240-2
SRPRAENST00000527817.1 linkn.635T>C non_coding_transcript_exon_variant Exon 5 of 5 2
SRPRAENST00000531104.1 linkn.431T>C non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152226
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251334
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152226
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000393
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Aug 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

SRPRA: PP3 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.44
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.52
D;.
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.030
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
0.20
D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Pathogenic
0.94
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.90
MutPred
0.73
Loss of sheet (P = 0.0126);.;
MVP
0.38
MPC
1.3
ClinPred
0.99
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.87
gMVP
0.92

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.

Other links and lift over

dbSNP: rs773233317; hg19: chr11-126135027; API