Variant NM_004596.5:c.240A>G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004596.5(SNRPA):c.240A>G(p.Lys80Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 1,609,030 control chromosomes in the GnomAD database, including 9,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.15 ( 2821 hom., cov: 30)

Exomes 𝑓: 0.084 ( 6962 hom. )

Consequence

SNRPA
NM_004596.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.93

Variant links:

Genes affected

SNRPA (HGNC:11151): (small nuclear ribonucleoprotein polypeptide A) The protein encoded by this gene associates with stem loop II of the U1 small nuclear ribonucleoprotein, which binds the 5' splice site of precursor mRNAs and is required for splicing. The encoded protein autoregulates itself by polyadenylation inhibition of its own pre-mRNA via dimerization and has been implicated in the coupling of splicing and polyadenylation. [provided by RefSeq, Oct 2010]

SNRPA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 19-40757498-A-G is Benign according to our data. Variant chr19-40757498-A-G is described in ClinVar as [Benign]. Clinvar id is 3056710.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPA	NM_004596.5 link	c.240A>G	p.Lys80Lys	synonymous_variant	Exon 2 of 6	ENST00000243563.8	NP_004587.1	P09012

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPA	ENST00000243563.8 link	c.240A>G	p.Lys80Lys	synonymous_variant	Exon 2 of 6	1	NM_004596.5	ENSP00000243563.2		P09012

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23246

AN:

151420

Hom.:

2792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.0585

Gnomad AMR

AF:

0.0754

Gnomad ASJ

AF:

0.0566

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.0637

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0716

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.101

AC:

24952

AN:

247650

Hom.:

1984

AF XY:

0.0953

AC XY:

12773

AN XY:

134010

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.0488

Gnomad ASJ exome

AF:

0.0623

Gnomad EAS exome

AF:

0.208

Gnomad SAS exome

AF:

0.0547

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.0743

Gnomad OTH exome

AF:

0.0811

GnomAD4 exome

AF:

0.0841

AC:

122642

AN:

1457492

Hom.:

6962

Cov.:

AF XY:

0.0825

AC XY:

59816

AN XY:

724912

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.0507

Gnomad4 ASJ exome

AF:

0.0620

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.0562

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.0726

Gnomad4 OTH exome

AF:

0.0976

GnomAD4 genome

AF:

0.154

AC:

23318

AN:

151538

Hom.:

2821

Cov.:

AF XY:

0.154

AC XY:

11359

AN XY:

73996

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.0752

Gnomad4 ASJ

AF:

0.0566

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.0629

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.0716

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0996

Hom.:

725

Bravo

AF:

0.158

Asia WGS

AF:

0.140

AC:

485

AN:

3478

EpiCase

AF:

0.0710

EpiControl

AF:

0.0689

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SNRPA-related disorder

Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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