rs7595

Positions:

• chr19-54193224-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001077446.4(TSEN34):​c.795T>C​(p.Pro265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,742 control chromosomes in the GnomAD database, including 34,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3517 hom., cov: 31)
  • Exomes 𝑓: 0.20 (31327 hom.)
• Consequence: TSEN34 NM_001077446.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.89

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-54193224-T-C is Benign according to our data. Variant chr19-54193224-T-C is described in ClinVar as [Benign]. Clinvar id is 1637899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN34	NM_001077446.4	c.795T>C	p.Pro265=	synonymous_variant	4/4	ENST00000396388.3	NP_001070914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN34	ENST00000396388.3	c.795T>C	p.Pro265=	synonymous_variant	4/4	1	NM_001077446.4	ENSP00000379671	P2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30845 AN: 151794 Hom.: 3512 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.196 AC: 287072 AN: 1461828 Hom.: 31327 Cov.: 34 AF XY: 0.196 AC XY: 142410 AN XY: 727214

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.468

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.203 AC: 30866 AN: 151914 Hom.: 3517 Cov.: 31 AF XY: 0.207 AC XY: 15387 AN XY: 74228

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.217

Alfa AF: 0.190 Hom.: 5261

Bravo AF: 0.211

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7595; hg19: chr19-54697079;