chr19-54191226-C-T

Position:

• chr19-54191226-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000302937.8(TSEN34):​c.-4-135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000718 in 1,433,784 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (3 hom.)
• Consequence: TSEN34 ENST00000302937.8 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.39

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 19-54191226-C-T is Benign according to our data. Variant chr19-54191226-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1216351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN34	NM_001282332.2	c.-4-135C>T		intron_variant			NP_001269261.1
TSEN34	NM_001282333.2	c.-4-135C>T		intron_variant			NP_001269262.2
TSEN34	NM_001386740.1	c.-4-135C>T		intron_variant			NP_001373669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN34	ENST00000302937.8	c.-4-135C>T		intron_variant		1		ENSP00000305524	P2
TSEN34	ENST00000396383.5	c.-4-135C>T		intron_variant		1		ENSP00000379667	P2
TSEN34	ENST00000429671.7	c.-4-135C>T		intron_variant		2		ENSP00000397402	P2

Frequencies

GnomAD3 genomes AF: 0.00310 AC: 471 AN: 151992 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000434 AC: 556 AN: 1281674 Hom.: 3 Cov.: 33 AF XY: 0.000385 AC XY: 241 AN XY: 626036

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.0000540

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000631

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.00312 AC: 474 AN: 152110 Hom.: 2 Cov.: 33 AF XY: 0.00269 AC XY: 200 AN XY: 74376

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00208 Hom.: 0

Bravo AF: 0.00379

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 05, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.18
DANN	Benign	0.94

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

LitVar

Other links and lift over

dbSNP: rs536602313; hg19: chr19-54695077;