Genetic Variant NM_003094.4:c.1A>T (chr1-203861660-A-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_003094.4(SNRPE):c.1A>T(p.Met1?) variant causes a initiator codon 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 initiator_codon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.80

Publications

0 publications found

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]

SNRPE Gene-Disease associations (from GenCC):

hypotrichosis 11
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypotrichosis simplex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SNRPE links:

ENSG00000297888 (HGNC:):

ENSG00000297888 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 14 codons. Genomic position: 203861699. Lost 0.143 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003094.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNRPE	NM_003094.4	MANE Select	c.1A>T	p.Met1?	initiator_codon	Exon 1 of 5	NP_003085.1	P62304
SNRPE	NM_001304464.2		c.-68A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001291393.1
SNRPE	NM_001304464.2		c.-68A>T		5_prime_UTR	Exon 1 of 5	NP_001291393.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNRPE	ENST00000414487.7	TSL:1 MANE Select	c.1A>T	p.Met1?	initiator_codon	Exon 1 of 5	ENSP00000400591.2	P62304
SNRPE	ENST00000475035.5	TSL:1	n.58A>T		non_coding_transcript_exon	Exon 1 of 5
SNRPE	ENST00000917033.1		c.1A>T	p.Met1?	initiator_codon	Exon 1 of 5	ENSP00000587092.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.56

MetaRNN

Pathogenic

0.92

MetaSVM

Benign

-0.29

PhyloP100

6.8

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.44

Sift

Uncertain

0.011

Sift4G

Pathogenic

0.0

Polyphen

0.70

Vest4

0.95

MutPred

0.66

Gain of stability (P = 0.0258)

MVP

0.88

ClinPred

0.99

GERP RS

5.6

PromoterAI

-0.45

Neutral

(source)

Varity_R

0.85

gMVP

0.71

Mutation Taster

=35/165

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over