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GeneBe

19-40765137-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004596.5(SNRPA):c.819C>T(p.Asn273=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,549,908 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

SNRPA
NM_004596.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-40765137-C-T is Benign according to our data. Variant chr19-40765137-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048078.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.23 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 103 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNRPANM_004596.5 linkuse as main transcriptc.819C>T p.Asn273= synonymous_variant 6/6 ENST00000243563.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNRPAENST00000243563.8 linkuse as main transcriptc.819C>T p.Asn273= synonymous_variant 6/61 NM_004596.5 P1
SNRPAENST00000601393.1 linkuse as main transcriptc.756C>T p.Asn252= synonymous_variant 6/63
SNRPAENST00000596860.1 linkuse as main transcriptn.265C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000677
AC:
103
AN:
152226
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00224
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000296
AC:
60
AN:
202548
Hom.:
0
AF XY:
0.000235
AC XY:
26
AN XY:
110758
show subpopulations
Gnomad AFR exome
AF:
0.00372
Gnomad AMR exome
AF:
0.000166
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000127
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000623
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000142
AC:
198
AN:
1397564
Hom.:
1
Cov.:
30
AF XY:
0.000141
AC XY:
98
AN XY:
693046
show subpopulations
Gnomad4 AFR exome
AF:
0.00321
Gnomad4 AMR exome
AF:
0.0000863
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000292
Gnomad4 SAS exome
AF:
0.000140
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000666
Gnomad4 OTH exome
AF:
0.000192
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000676
AC:
103
AN:
152344
Hom.:
0
Cov.:
32
AF XY:
0.000711
AC XY:
53
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00224
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000588
Hom.:
0
Bravo
AF:
0.000846

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SNRPA-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 18, 2019This variant is classified as likely 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
-0.69
Cadd
Benign
0.27
Dann
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs142041325; hg19: chr19-41271042; COSMIC: COSV99698963; COSMIC: COSV99698963; API