2-45418518-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.2180A>Gā€‹(p.Asn727Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 151,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)

Consequence

SRBD1
NM_018079.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80
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=0.102596164).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SRBD1NM_018079.5 linkuse as main transcriptc.2180A>G p.Asn727Ser missense_variant 18/21 ENST00000263736.5 NP_060549.4
SRBD1XM_011532946.3 linkuse as main transcriptc.2132A>G p.Asn711Ser missense_variant 18/21 XP_011531248.1
SRBD1XM_047444861.1 linkuse as main transcriptc.737A>G p.Asn246Ser missense_variant 10/13 XP_047300817.1
SRBD1XM_047444862.1 linkuse as main transcriptc.737A>G p.Asn246Ser missense_variant 9/12 XP_047300818.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SRBD1ENST00000263736.5 linkuse as main transcriptc.2180A>G p.Asn727Ser missense_variant 18/212 NM_018079.5 ENSP00000263736 P1Q8N5C6-1
SRBD1ENST00000475073.5 linkuse as main transcriptn.504A>G non_coding_transcript_exon_variant 6/64
SRBD1ENST00000490133.5 linkuse as main transcriptn.1077A>G non_coding_transcript_exon_variant 3/62

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151958
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.000478
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151958
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74236
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000131
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:
0.000478
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000529

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 GeneticsAug 02, 2021The c.2180A>G (p.N727S) alteration is located in exon 18 (coding exon 17) of the SRBD1 gene. This alteration results from a A to G substitution at nucleotide position 2180, causing the asparagine (N) at amino acid position 727 to be replaced by a serine (S). 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
0.049
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
19
DANN
Benign
0.44
DEOGEN2
Benign
0.00032
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.035
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.4
N
MutationTaster
Benign
0.97
N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.43
N
REVEL
Benign
0.047
Sift
Benign
0.74
T
Sift4G
Benign
1.0
T
Polyphen
0.097
B
Vest4
0.21
MutPred
0.30
Loss of stability (P = 0.1288);
MVP
0.43
MPC
0.015
ClinPred
0.37
T
GERP RS
4.8
Varity_R
0.042
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs1406493564; hg19: chr2-45645657; API