2-45392973-G-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.2670C>Gā€‹(p.Ser890Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000302 in 1,459,338 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: not found (cov: 32)
Exomes š‘“: 0.000030 ( 0 hom. )

Consequence

SRBD1
NM_018079.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.209
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=0.10893315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SRBD1NM_018079.5 linkuse as main transcriptc.2670C>G p.Ser890Arg missense_variant 20/21 ENST00000263736.5 NP_060549.4
SRBD1XM_011532946.3 linkuse as main transcriptc.2622C>G p.Ser874Arg missense_variant 20/21 XP_011531248.1
SRBD1XM_047444861.1 linkuse as main transcriptc.1227C>G p.Ser409Arg missense_variant 12/13 XP_047300817.1
SRBD1XM_047444862.1 linkuse as main transcriptc.1227C>G p.Ser409Arg missense_variant 11/12 XP_047300818.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SRBD1ENST00000263736.5 linkuse as main transcriptc.2670C>G p.Ser890Arg missense_variant 20/212 NM_018079.5 ENSP00000263736 P1Q8N5C6-1
SRBD1ENST00000490133.5 linkuse as main transcriptn.1567C>G non_coding_transcript_exon_variant 5/62

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
249698
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134868
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000302
AC:
44
AN:
1459338
Hom.:
0
Cov.:
30
AF XY:
0.0000317
AC XY:
23
AN XY:
725602
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

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 GeneticsDec 27, 2023The c.2670C>G (p.S890R) alteration is located in exon 20 (coding exon 19) of the SRBD1 gene. This alteration results from a C to G substitution at nucleotide position 2670, causing the serine (S) at amino acid position 890 to be replaced by an arginine (R). 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
0.21
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0032
T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
0.69
D;D
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.074
Sift
Benign
0.052
T
Sift4G
Benign
0.068
T
Polyphen
0.0
B
Vest4
0.29
MutPred
0.36
Gain of sheet (P = 0.0149);
MVP
0.26
MPC
0.013
ClinPred
0.48
T
GERP RS
-0.45
Varity_R
0.088
gMVP
0.81

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: rs865875771; hg19: chr2-45620112; API