NM_004596.5:c.689+475T>G

Variant names:

• chr19-40764150-T-G
• rs17713068
• NM_004596.5:c.689+475T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004596.5(SNRPA):​c.689+475T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,016 control chromosomes in the GnomAD database, including 1,285 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1285 hom., cov: 32)
• Consequence: SNRPA NM_004596.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004596.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPA	NM_004596.5	MANE Select	c.689+475T>G		intron	N/A	NP_004587.1	P09012

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPA	ENST00000243563.8	TSL:1 MANE Select	c.689+475T>G		intron	N/A	ENSP00000243563.2	P09012
	SNRPA	ENST00000925562.1		c.821+475T>G		intron	N/A	ENSP00000595621.1
	SNRPA	ENST00000861888.1		c.782+475T>G		intron	N/A	ENSP00000531947.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18374 AN: 151898 Hom.: 1280 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 18398 AN: 152016 Hom.: 1285 Cov.: 32 AF XY: 0.122 AC XY: 9078 AN XY: 74328

African (AFR) AF: 0.0707 AC: 2931 AN: 41448

American (AMR) AF: 0.136 AC: 2078 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3468

East Asian (EAS) AF: 0.0797 AC: 412 AN: 5170

South Asian (SAS) AF: 0.185 AC: 891 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1475 AN: 10586

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9896 AN: 67966

Other (OTH) AF: 0.114 AC: 241 AN: 2108

Alfa AF: 0.137 Hom.: 574

Bravo AF: 0.115

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.49
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17713068; hg19: chr19-41270055;