ENST00000302937.8:c.-4-66G>A

Variant names:

• chr19-54191295-G-A
• rs532178295
• ENST00000302937.8:c.-4-66G>A

Variant summary

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

The ENST00000302937.8(TSEN34):​c.-4-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,544,452 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (16 hom.)
• Consequence: TSEN34 ENST00000302937.8 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.655

Genes affected

TSEN34 (HGNC:15506): (tRNA splicing endonuclease subunit 34) This gene encodes a catalytic subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from precursor tRNAs. The endonuclease complex is also associated with a pre-mRNA 3-prime end processing factor. A mutation in this gene results in the neurological disorder pontocerebellar hypoplasia type 2. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-54191295-G-A is Benign according to our data. Variant chr19-54191295-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 679020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN34	NM_001077446.4	c.-70G>A		upstream_gene_variant		ENST00000396388.3	NP_001070914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN34	ENST00000396388.3	c.-70G>A		upstream_gene_variant		1	NM_001077446.4	ENSP00000379671.2

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 388 AN: 152084 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000633

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00138 AC: 1920 AN: 1392260 Hom.: 16 Cov.: 34 AF XY: 0.00146 AC XY: 1004 AN XY: 686752

Gnomad4 AFR exome AF: 0.0000322

Gnomad4 AMR exome AF: 0.000985

Gnomad4 ASJ exome AF: 0.000400

Gnomad4 EAS exome AF: 0.0000282

Gnomad4 SAS exome AF: 0.00507

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.000417

Gnomad4 OTH exome AF: 0.000954

GnomAD4 genome AF: 0.00254 AC: 387 AN: 152192 Hom.: 4 Cov.: 33 AF XY: 0.00380 AC XY: 283 AN XY: 74400

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.000633

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000567

Asia WGS AF: 0.00145 AC: 5 AN: 3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs532178295; hg19: chr19-54695146; COSMIC: COSV55475890; COSMIC: COSV55475890;