19-40765137-C-T

Variant names:

• chr19-40765137-C-T
• rs142041325
• NM_004596.5:c.819C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_004596.5(SNRPA):​c.819C>T​(p.Asn273Asn) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: SNRPA NM_004596.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.23

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: 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 no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.23 with no splicing effect.
• BS2: High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPA	NM_004596.5	c.819C>T	p.Asn273Asn	synonymous_variant	Exon 6 of 6	ENST00000243563.8	NP_004587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPA	ENST00000243563.8	c.819C>T	p.Asn273Asn	synonymous_variant	Exon 6 of 6	1	NM_004596.5	ENSP00000243563.2
SNRPA	ENST00000601393.1	c.756C>T	p.Asn252Asn	synonymous_variant	Exon 6 of 6	3		ENSP00000472355.1
SNRPA	ENST00000596860.1	n.265C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
SNRPA	ENST00000601545.5	c.*116C>T		downstream_gene_variant		5		ENSP00000470534.1

Frequencies

GnomAD3 genomes AF: 0.000677 AC: 103 AN: 152226 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000296 AC: 60 AN: 202548 AF XY: 0.000235

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 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

Gnomad4 AFR exome AF: 0.00321 AC: 96 AN: 29940

Gnomad4 AMR exome AF: 0.0000863 AC: 3 AN: 34754

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 24372

Gnomad4 EAS exome AF: 0.0000292 AC: 1 AN: 34236

Gnomad4 SAS exome AF: 0.000140 AC: 11 AN: 78322

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52636

Gnomad4 NFE exome AF: 0.0000666 AC: 72 AN: 1080298

Gnomad4 Remaining exome AF: 0.000192 AC: 11 AN: 57426

GnomAD4 genome AF: 0.000676 AC: 103 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.000711 AC XY: 53 AN XY: 74492

Gnomad4 AFR AF: 0.00224 AC: 0.00223622 AN: 0.00223622

Gnomad4 AMR AF: 0.000196 AC: 0.000196053 AN: 0.000196053

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000193 AC: 0.000192827 AN: 0.000192827

Gnomad4 SAS AF: 0.000414 AC: 0.000414422 AN: 0.000414422

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000441 AC: 0.0000440995 AN: 0.0000440995

Gnomad4 OTH AF: 0.000473 AC: 0.000473037 AN: 0.000473037

Alfa AF: 0.000588 Hom.: 0

Bravo AF: 0.000846

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SNRPA-related disorder Benign:1

Feb 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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

Other links and lift over

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