1-203861660-A-T

Variant names:

• chr1-203861660-A-T
• rs587776924
• NM_003094.4:c.1A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001304464.2(SNRPE):​c.-68A>T variant causes a 5 prime UTR premature start codon gain 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_001304464.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.80
• Publications: 0 publications found

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

ENSG00000297888 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304464.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	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

Sel.	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.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.56	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.29	T
PhyloP100		6.8
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.70	P
Vest4		0.95
MutPred		0.66		Gain of stability (P = 0.0258)
MVP		0.88
ClinPred		0.99	D
GERP RS		5.6
PromoterAI		-0.45	Neutral
Varity_R		0.85
gMVP		0.71
Mutation Taster		=35/165	disease causing

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

Other links and lift over

dbSNP: rs587776924; hg19: chr1-203830788;