chr19-54191437-C-G

Variant names:

• chr19-54191437-C-G
• rs1307925755
• NM_001077446.4:c.73C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001077446.4(TSEN34):​c.73C>G​(p.Arg25Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSEN34 NM_001077446.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2771774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN34	NM_001077446.4	c.73C>G	p.Arg25Gly	missense_variant	Exon 1 of 4	ENST00000396388.3	NP_001070914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN34	ENST00000396388.3	c.73C>G	p.Arg25Gly	missense_variant	Exon 1 of 4	1	NM_001077446.4	ENSP00000379671.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000705 AC: 1 AN: 141882 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76808

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000436

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.17e-7 AC: 1 AN: 1395646 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 688542

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	.;T;T;.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.29	N
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	.;.;M;.;M;M
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-2.2	N;N;N;.;N;N
REVEL	Benign	0.19
Sift	Benign	0.38	T;T;T;.;T;T
Sift4G	Uncertain	0.016	D;T;T;D;T;T
Polyphen		0.98	.;.;D;.;D;D
Vest4		0.33, 0.32, 0.33, 0.24
MutPred		0.31		Loss of stability (P = 0.0152);.;Loss of stability (P = 0.0152);.;Loss of stability (P = 0.0152);Loss of stability (P = 0.0152);
MVP		0.66
MPC		0.98
ClinPred		0.86	D
GERP RS		2.9
Varity_R		0.24
gMVP		0.61

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: rs1307925755; hg19: chr19-54695288;