19-54191122-A-A

Variant names:

• chr19-54191122-A-A
• ENST00000396388.3:c.

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 6P and 8B. PVS1_Strong PM2 BP6_Very_Strong

The ENST00000396388.3(TSEN34):​c. variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSEN34 ENST00000396388.3 splice_donor, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.55

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 Likely_benign. Variant got -2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.3215434 fraction of the gene.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-54191122-A-A is Benign according to our data. Variant chr19-54191122-A-A is described in ClinVar as [Benign]. Clinvar id is 1264043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN34		n.		intragenic_variant
TSEN34	NM_001077446.4	c.		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.		splice_donor_variant, intron_variant	Intron 2 of 3	1	NM_001077446.4	ENSP00000379671.2
TSEN34	ENST00000396388.3	c.		upstream_gene_variant		1	NM_001077446.4	ENSP00000379671.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54694973;