1-203861932-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003094.4(SNRPE):c.54+219C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00631 in 613,250 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (15 hom.)
• Consequence: SNRPE NM_003094.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.92

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-203861932-C-T is Benign according to our data. Variant chr1-203861932-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038971.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 834 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRPE	NM_003094.4	c.54+219C>T		intron_variant		ENST00000414487.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPE	ENST00000414487.7	c.54+219C>T		intron_variant		1	NM_003094.4	P1

Frequencies

GnomAD3 genomes AF: 0.00548 AC: 834 AN: 152088 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00856

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00658 AC: 3034 AN: 461044 Hom.: 15 Cov.: 4 AF XY: 0.00624 AC XY: 1520 AN XY: 243410

Gnomad4 AFR exome AF: 0.00182

Gnomad4 AMR exome AF: 0.00249

Gnomad4 ASJ exome AF: 0.00418

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.00903

Gnomad4 NFE exome AF: 0.00872

Gnomad4 OTH exome AF: 0.00565

GnomAD4 genome AF: 0.00548 AC: 834 AN: 152206 Hom.: 3 Cov.: 32 AF XY: 0.00519 AC XY: 386 AN XY: 74402

Gnomad4 AFR AF: 0.00176

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.00856

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00789 Hom.: 1

Bravo AF: 0.00462

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SNRPE-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 24, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.95
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs183028927; hg19: chr1-203831060;