19-40759588-G-C

Variant names:

• chr19-40759588-G-C
• rs2082923055
• NM_004596.5:c.404G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004596.5(SNRPA):​c.404G>C​(p.Gly135Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SNRPA NM_004596.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.283
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070353985).

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.404G>C	p.Gly135Ala	missense	Exon 3 of 6	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.404G>C	p.Gly135Ala	missense	Exon 3 of 6	ENSP00000243563.2	P09012
	SNRPA	ENST00000925562.1		c.536G>C	p.Gly179Ala	missense	Exon 4 of 7	ENSP00000595621.1
	SNRPA	ENST00000861888.1		c.497G>C	p.Gly166Ala	missense	Exon 4 of 7	ENSP00000531947.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Benign	0.30
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.27	N
PhyloP100		0.28
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.079
Sift	Benign	0.61	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.27		Gain of helix (P = 0.0854)
MVP		0.31
MPC		0.63
ClinPred		0.066	T
GERP RS		4.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1
Varity_R		0.079
gMVP		0.32
Mutation Taster		=83/17	polymorphism

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: rs2082923055; hg19: chr19-41265493;