NM_052965.4:c.192C>G

Variant names:

• chr1-184054410-C-G
• NM_052965.4:c.192C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052965.4(TSEN15):​c.192C>G​(p.Phe64Leu) variant causes a missense 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSEN15 NM_052965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.840

Genes affected

TSEN15 (HGNC:16791): (tRNA splicing endonuclease subunit 15) This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN15	NM_052965.4	c.192C>G	p.Phe64Leu	missense_variant	Exon 2 of 5	ENST00000645668.2	NP_443197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN15	ENST00000645668.2	c.192C>G	p.Phe64Leu	missense_variant	Exon 2 of 5		NM_052965.4	ENSP00000493902.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pontocerebellar hypoplasia, type 2F Uncertain:1

Mar 11, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;.;.;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M;M;.;.;.;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.9	.;D;D;.;D;.;.
REVEL	Benign	0.28
Sift	Uncertain	0.026	.;D;D;.;D;.;.
Sift4G	Benign	0.082	.;T;T;.;T;.;.
Polyphen		1.0	D;.;.;.;.;.;.
Vest4		0.74, 0.62, 0.75
MutPred		0.75		Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);
MVP		0.31
MPC		1.5
ClinPred		0.98	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-184023544;