rs2230694

Variant names:

• chr19-40757498-A-C
• rs2230694
• NM_004596.5:c.240A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-40757498-A-C
• chr19-40757498-A-G
• chr19-40757498-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004596.5(SNRPA):​c.240A>C​(p.Lys80Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SNRPA NM_004596.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPA	NM_004596.5	c.240A>C	p.Lys80Asn	missense_variant	Exon 2 of 6	ENST00000243563.8	NP_004587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPA	ENST00000243563.8	c.240A>C	p.Lys80Asn	missense_variant	Exon 2 of 6	1	NM_004596.5	ENSP00000243563.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;T;.;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.3	.;M;.;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.6	.;D;.;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.0050	.;D;.;.;.
Sift4G	Uncertain	0.015	D;D;D;D;D
Polyphen		0.84	.;P;.;.;.
Vest4		0.78
MutPred		0.58		.;Loss of methylation at K80 (P = 0.0193);Loss of methylation at K80 (P = 0.0193);Loss of methylation at K80 (P = 0.0193);Loss of methylation at K80 (P = 0.0193);
MVP		0.46
MPC		1.4
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.88
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2230694; hg19: chr19-41263403;