2-45418432-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018079.5(SRBD1):ā€‹c.2266C>Gā€‹(p.Pro756Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

SRBD1
NM_018079.5 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.46
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SRBD1NM_018079.5 linkuse as main transcriptc.2266C>G p.Pro756Ala missense_variant 18/21 ENST00000263736.5 NP_060549.4
SRBD1XM_011532946.3 linkuse as main transcriptc.2218C>G p.Pro740Ala missense_variant 18/21 XP_011531248.1
SRBD1XM_047444861.1 linkuse as main transcriptc.823C>G p.Pro275Ala missense_variant 10/13 XP_047300817.1
SRBD1XM_047444862.1 linkuse as main transcriptc.823C>G p.Pro275Ala 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.2266C>G p.Pro756Ala missense_variant 18/212 NM_018079.5 ENSP00000263736 P1Q8N5C6-1
SRBD1ENST00000490133.5 linkuse as main transcriptn.1163C>G non_coding_transcript_exon_variant 3/62
SRBD1ENST00000475073.5 linkuse as main transcript downstream_gene_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251440
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461832
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
727214
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:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsJan 26, 2022The c.2266C>G (p.P756A) alteration is located in exon 18 (coding exon 17) of the SRBD1 gene. This alteration results from a C to G substitution at nucleotide position 2266, causing the proline (P) at amino acid position 756 to be replaced by an alanine (A). 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
0.10
BayesDel_addAF
Benign
-0.087
T
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.084
T
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.72
D
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.80
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-4.0
D
REVEL
Uncertain
0.30
Sift
Uncertain
0.011
D
Sift4G
Uncertain
0.058
T
Polyphen
1.0
D
Vest4
0.80
MutPred
0.40
Gain of MoRF binding (P = 0.036);
MVP
0.69
MPC
0.099
ClinPred
0.85
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.25
gMVP
0.60

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: rs771083985; hg19: chr2-45645571; API