Variant chr2-45418518-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018079.5(SRBD1):c.2180A>G(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 (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Consequence

SRBD1
NM_018079.5 missense

Scores

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]

SRBD1 links:

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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
SRBD1	NM_018079.5 linkuse as main transcript	c.2180A>G	p.Asn727Ser	missense_variant	18/21	ENST00000263736.5
SRBD1	XM_011532946.3 linkuse as main transcript	c.2132A>G	p.Asn711Ser	missense_variant	18/21
SRBD1	XM_047444861.1 linkuse as main transcript	c.737A>G	p.Asn246Ser	missense_variant	10/13
SRBD1	XM_047444862.1 linkuse as main transcript	c.737A>G	p.Asn246Ser	missense_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRBD1	ENST00000263736.5 linkuse as main transcript	c.2180A>G	p.Asn727Ser	missense_variant	18/21	2	NM_018079.5	P1	Q8N5C6-1
SRBD1	ENST00000475073.5 linkuse as main transcript	n.504A>G		non_coding_transcript_exon_variant	6/6	4
SRBD1	ENST00000490133.5 linkuse as main transcript	n.1077A>G		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151958

Hom.:

Cov.:

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.:

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151958

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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 submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The 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

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.44

DEOGEN2

Benign

0.00032

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0079

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

MutationTaster

Benign

0.97

N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.43

REVEL

Benign

0.047

Sift

Benign

0.74

Sift4G

Benign

1.0

Polyphen

0.097

Vest4

0.21

MutPred

0.30

Loss of stability (P = 0.1288);

MVP

0.43

MPC

0.015

ClinPred

0.37

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over