chr1-203861660-A-T
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PS1_ModeratePM2
The NM_003094.4(SNRPE):c.1A>T(p.Met1?) variant causes a start lost change. 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SNRPE
NM_003094.4 start_lost
NM_003094.4 start_lost
Scores
5
6
5
Clinical Significance
Conservation
PhyloP100: 6.80
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 Pathogenic. Variant got 12 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PS1
Another start lost variant in NM_003094.4 (SNRPE) was described as [Likely_pathogenic] in ClinVar as 39505
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNRPE | NM_003094.4 | c.1A>T | p.Met1? | start_lost | 1/5 | ENST00000414487.7 | |
SNRPE | NM_001304464.2 | c.-68A>T | 5_prime_UTR_variant | 1/5 | |||
SNRPE | NR_130746.2 | n.62A>T | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNRPE | ENST00000414487.7 | c.1A>T | p.Met1? | start_lost | 1/5 | 1 | NM_003094.4 | P1 | |
SNRPE | ENST00000475035.5 | n.58A>T | non_coding_transcript_exon_variant | 1/5 | 1 | ||||
SNRPE | ENST00000470492.5 | n.52A>T | non_coding_transcript_exon_variant | 1/4 | 3 | ||||
SNRPE | ENST00000483099.5 | n.58A>T | non_coding_transcript_exon_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Disruption of the initiator codon has been observed in individual(s) with hypotrichosis simplex (PMID: 23246290). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SNRPE mRNA. The next in-frame methionine is located at codon 14. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationTaster
Benign
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Gain of stability (P = 0.0258);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.