2-45488246-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018079.5(SRBD1):ā€‹c.1960A>Gā€‹(p.Ser654Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,613,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

SRBD1
NM_018079.5 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.95
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 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=0.23367774).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SRBD1NM_018079.5 linkuse as main transcriptc.1960A>G p.Ser654Gly missense_variant 15/21 ENST00000263736.5 NP_060549.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SRBD1ENST00000263736.5 linkuse as main transcriptc.1960A>G p.Ser654Gly missense_variant 15/212 NM_018079.5 ENSP00000263736 P1Q8N5C6-1
SRBD1ENST00000475073.5 linkuse as main transcriptn.367A>G non_coding_transcript_exon_variant 4/64

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152200
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
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:
0.0000757
AC:
19
AN:
251150
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135730
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00103
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:
0.00000958
AC:
14
AN:
1461514
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727064
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000328
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152200
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
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:
0.0000741
AC:
9

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 GeneticsJun 07, 2023The c.1960A>G (p.S654G) alteration is located in exon 15 (coding exon 14) of the SRBD1 gene. This alteration results from a A to G substitution at nucleotide position 1960, causing the serine (S) at amino acid position 654 to be replaced by a glycine (G). 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
0.33
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.079
T
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.61
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.24
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.60
P
Vest4
0.78
MutPred
0.30
Gain of methylation at R653 (P = 0.0528);
MVP
0.40
MPC
0.037
ClinPred
0.36
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.81
gMVP
0.80

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: rs765156998; hg19: chr2-45715385; COSMIC: COSV105846441; API