chr19-40759474-T-C

Variant summary

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

The NM_004596.5(SNRPA):ā€‹c.290T>Cā€‹(p.Met97Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SNRPA
NM_004596.5 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
SNRPANM_004596.5 linkuse as main transcriptc.290T>C p.Met97Thr missense_variant 3/6 ENST00000243563.8 NP_004587.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNRPAENST00000243563.8 linkuse as main transcriptc.290T>C p.Met97Thr missense_variant 3/61 NM_004596.5 ENSP00000243563 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461842
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsDec 19, 2023The c.290T>C (p.M97T) alteration is located in exon 3 (coding exon 3) of the SNRPA gene. This alteration results from a T to C substitution at nucleotide position 290, causing the methionine (M) at amino acid position 97 to be replaced by a threonine (T). 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
Pathogenic
0.76
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Benign
0.17
.;T;.;T;.;.
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.52
D;D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
.;M;.;.;.;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-2.0
.;N;.;.;.;.
REVEL
Benign
0.20
Sift
Benign
0.20
.;T;.;.;.;.
Sift4G
Uncertain
0.031
D;T;T;T;T;T
Polyphen
0.19
.;B;.;.;.;.
Vest4
0.83
MutPred
0.38
.;Gain of methylation at K96 (P = 0.0258);.;Gain of methylation at K96 (P = 0.0258);Gain of methylation at K96 (P = 0.0258);.;
MVP
0.61
MPC
0.82
ClinPred
0.82
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.72
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-41265379; API