2-45413183-T-G

Variant summary

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

The NM_018079.5(SRBD1):ā€‹c.2444A>Cā€‹(p.Asn815Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,808 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‘“: 0.0000048 ( 0 hom. )

Consequence

SRBD1
NM_018079.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.145
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=0.17329013).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SRBD1NM_018079.5 linkuse as main transcriptc.2444A>C p.Asn815Thr missense_variant 19/21 ENST00000263736.5 NP_060549.4
SRBD1XM_011532946.3 linkuse as main transcriptc.2396A>C p.Asn799Thr missense_variant 19/21 XP_011531248.1
SRBD1XM_047444861.1 linkuse as main transcriptc.1001A>C p.Asn334Thr missense_variant 11/13 XP_047300817.1
SRBD1XM_047444862.1 linkuse as main transcriptc.1001A>C p.Asn334Thr 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.2444A>C p.Asn815Thr missense_variant 19/212 NM_018079.5 ENSP00000263736 P1Q8N5C6-1
SRBD1ENST00000490133.5 linkuse as main transcriptn.1341A>C non_coding_transcript_exon_variant 4/62

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251356
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
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:
0.00000479
AC:
7
AN:
1461808
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000264
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 GeneticsMar 29, 2024The c.2444A>C (p.N815T) alteration is located in exon 19 (coding exon 18) of the SRBD1 gene. This alteration results from a A to C substitution at nucleotide position 2444, causing the asparagine (N) at amino acid position 815 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
-0.42
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
5.8
DANN
Benign
0.96
DEOGEN2
Benign
0.0076
T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.032
Sift
Benign
0.035
D
Sift4G
Benign
0.49
T
Polyphen
0.10
B
Vest4
0.20
MutPred
0.71
Gain of sheet (P = 0.0149);
MVP
0.28
MPC
0.013
ClinPred
0.090
T
GERP RS
-0.81
Varity_R
0.073
gMVP
0.21

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: rs962403703; hg19: chr2-45640322; COSMIC: COSV105052409; API