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rs587776925

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_003094.4(SNRPE):c.133G>A(p.Gly45Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G45G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

SNRPE
NM_003094.4 missense

Scores

11
6
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.59
Variant links:
Genes affected
SNRPE (HGNC:11161): (small nuclear ribonucleoprotein polypeptide E) The protein encoded by this gene is a core component of U small nuclear ribonucleoproteins, which are key components of the pre-mRNA processing spliceosome. The encoded protein plays a role in the 3' end processing of histone transcripts. This protein is one of the targets in the autoimmune disease systemic lupus erythematosus, and mutations in this gene have been associated with hypotrichosis. Several pseudogenes of this gene have been identified. [provided by RefSeq, Jun 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.995
PP5
Variant 1-203863714-G-A is Pathogenic according to our data. Variant chr1-203863714-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 39506.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNRPENM_003094.4 linkuse as main transcriptc.133G>A p.Gly45Ser missense_variant 3/5 ENST00000414487.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNRPEENST00000414487.7 linkuse as main transcriptc.133G>A p.Gly45Ser missense_variant 3/51 NM_003094.4 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Hypotrichosis 11 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 10, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
Cadd
Pathogenic
32
Dann
Uncertain
1.0
DEOGEN2
Pathogenic
0.93
D;D
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Pathogenic
0.93
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Uncertain
0.69
D
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-5.7
D;D
REVEL
Pathogenic
0.95
Sift
Uncertain
0.015
D;D
Sift4G
Uncertain
0.016
D;D
Polyphen
0.94
P;.
Vest4
0.94
MutPred
0.96
Loss of catalytic residue at I43 (P = 0.2434);.;
MVP
0.98
MPC
1.5
ClinPred
1.0
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.90
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs587776925; hg19: chr1-203832842; API