chr2-45413256-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018079.5(SRBD1):​c.2371G>A​(p.Ala791Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SRBD1
NM_018079.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0550
Variant links:
Genes affected
SRBD1 (HGNC:25521): (S1 RNA binding domain 1) Predicted to enable mRNA binding activity. Predicted to be a structural constituent of ribosome. Predicted to be involved in translation. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.054099083).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SRBD1NM_018079.5 linkuse as main transcriptc.2371G>A p.Ala791Thr missense_variant 19/21 ENST00000263736.5 NP_060549.4
SRBD1XM_011532946.3 linkuse as main transcriptc.2323G>A p.Ala775Thr missense_variant 19/21 XP_011531248.1
SRBD1XM_047444861.1 linkuse as main transcriptc.928G>A p.Ala310Thr missense_variant 11/13 XP_047300817.1
SRBD1XM_047444862.1 linkuse as main transcriptc.928G>A p.Ala310Thr missense_variant 10/12 XP_047300818.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SRBD1ENST00000263736.5 linkuse as main transcriptc.2371G>A p.Ala791Thr missense_variant 19/212 NM_018079.5 ENSP00000263736 P1Q8N5C6-1
SRBD1ENST00000490133.5 linkuse as main transcriptn.1268G>A non_coding_transcript_exon_variant 4/62

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152208
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
250936
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135590
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000982
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000706
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461662
Hom.:
0
Cov.:
31
AF XY:
0.0000316
AC XY:
23
AN XY:
727116
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:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000486
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000656
AC:
10
AN:
152326
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsOct 05, 2022The c.2371G>A (p.A791T) alteration is located in exon 19 (coding exon 18) of the SRBD1 gene. This alteration results from a G to A substitution at nucleotide position 2371, causing the alanine (A) at amino acid position 791 to be replaced by a threonine (T). 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
0.067
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
14
DANN
Benign
0.56
DEOGEN2
Benign
0.0020
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.054
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.79
N
REVEL
Benign
0.032
Sift
Benign
0.24
T
Sift4G
Benign
0.56
T
Polyphen
0.0
B
Vest4
0.081
MVP
0.27
MPC
0.013
ClinPred
0.015
T
GERP RS
1.6
Varity_R
0.038
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs142081663; hg19: chr2-45640395; API