Variant 19-40762911-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004596.5(SNRPA):c.437C>T(p.Pro146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SNRPA
NM_004596.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

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]

SNRPA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25801688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRPA	NM_004596.5 linkuse as main transcript	c.437C>T	p.Pro146Leu	missense_variant	4/6	ENST00000243563.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPA	ENST00000243563.8 linkuse as main transcript	c.437C>T	p.Pro146Leu	missense_variant	4/6	1	NM_004596.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246248

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000910

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461344

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.437C>T (p.P146L) alteration is located in exon 4 (coding exon 4) of the SNRPA gene. This alteration results from a C to T substitution at nucleotide position 437, causing the proline (P) at amino acid position 146 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

Sift4G

Benign

0.30

T;T;D;T

Polyphen

0.95

.;P;.;.

Vest4

0.64

MutPred

0.30

.;Loss of catalytic residue at P145 (P = 0.0168);Loss of catalytic residue at P145 (P = 0.0168);.;

MVP

0.75

MPC

0.62

ClinPred

0.63

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.052

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over