chr19-54191203-G-T

Variant names:

• chr19-54191203-G-T
• rs58123079
• ENST00000302937.8:c.-4-158G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282333.2(TSEN34):​c.-4-158G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,384,726 control chromosomes in the GnomAD database, including 422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (53 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (369 hom.)
• Consequence: TSEN34 NM_001282333.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.88
• Publications: 0 publications found

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]

TSEN34 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2C

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• pontocerebellar hypoplasia type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-54191203-G-T is Benign according to our data. Variant chr19-54191203-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1217402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282333.2. 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
	TSEN34	NM_001282333.2		c.-4-158G>T		intron	N/A	NP_001269262.2	A0A590UJW4
	TSEN34	NM_001282332.2		c.-4-158G>T		intron	N/A	NP_001269261.1	Q9BSV6
	TSEN34	NM_001386740.1		c.-4-158G>T		intron	N/A	NP_001373669.1	Q9BSV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN34	ENST00000302937.8	TSL:1	c.-4-158G>T		intron	N/A	ENSP00000305524.4	Q9BSV6
	TSEN34	ENST00000396383.5	TSL:1	c.-4-158G>T		intron	N/A	ENSP00000379667.1	Q9BSV6
	TSEN34	ENST00000667261.1		c.-4-158G>T		intron	N/A	ENSP00000499595.1	A0A590UJW4

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1973 AN: 151780 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.00565 AC: 6971 AN: 1232826 Hom.: 369 Cov.: 33 AF XY: 0.00556 AC XY: 3327 AN XY: 597898

African (AFR) AF: 0.0160 AC: 374 AN: 23430

American (AMR) AF: 0.0227 AC: 318 AN: 14014

Ashkenazi Jewish (ASJ) AF: 0.00250 AC: 42 AN: 16802

East Asian (EAS) AF: 0.144 AC: 4219 AN: 29356

South Asian (SAS) AF: 0.00324 AC: 181 AN: 55912

European-Finnish (FIN) AF: 0.0278 AC: 899 AN: 32302

Middle Eastern (MID) AF: 0.000584 AC: 2 AN: 3424

European-Non Finnish (NFE) AF: 0.000352 AC: 355 AN: 1007114

Other (OTH) AF: 0.0115 AC: 581 AN: 50472

GnomAD4 genome AF: 0.0131 AC: 1983 AN: 151900 Hom.: 53 Cov.: 33 AF XY: 0.0148 AC XY: 1096 AN XY: 74246

African (AFR) AF: 0.0167 AC: 694 AN: 41476

American (AMR) AF: 0.0154 AC: 236 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3466

East Asian (EAS) AF: 0.116 AC: 586 AN: 5068

South Asian (SAS) AF: 0.00852 AC: 41 AN: 4812

European-Finnish (FIN) AF: 0.0304 AC: 322 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 67876

Other (OTH) AF: 0.0133 AC: 28 AN: 2108

Alfa AF: 0.00343 Hom.: 2

Bravo AF: 0.0135

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.14
DANN	Benign	0.79
PhyloP100		-1.9
PromoterAI		-0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs58123079; hg19: chr19-54695054;