Variant 4-8441043-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152544.3(TRMT44):c.221C>T(p.Pro74Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,338,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

TRMT44
NM_152544.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.262

Variant links:

Genes affected

TRMT44 (HGNC:26653): (tRNA methyltransferase 44 homolog) The protein encoded by this gene is a putative tRNA methyltransferase found in the cytoplasm. Defects in this gene may be a cause of partial epilepsy with pericentral spikes (PEPS), but that has not been proven definitively. [provided by RefSeq, May 2012]

TRMT44 links:

TRMT44 (HGNC:):

TRMT44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11484495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT44	NM_152544.3 linkuse as main transcript	c.221C>T	p.Pro74Leu	missense_variant	1/11	ENST00000389737.5	NP_689757.2	Q8IYL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRMT44	ENST00000389737.5 linkuse as main transcript	c.221C>T	p.Pro74Leu	missense_variant	1/11	5	NM_152544.3	ENSP00000374387.4	Q8IYL2-1
TRMT44	ENST00000513449.6 linkuse as main transcript	c.-76+2001C>T		intron_variant		1		ENSP00000424643.2	Q8IYL2-2
TRMT44	ENST00000504134.1 linkuse as main transcript	c.80C>T	p.Pro27Leu	missense_variant	1/2	3		ENSP00000434207.1	H0YDS2
TRMT44	ENST00000528167.1 linkuse as main transcript	n.239C>T		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000104

AC:

AN:

96120

Hom.:

AF XY:

0.00

AC XY:

AN XY:

51980

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000252

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.47e-7

AC:

AN:

1338346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

656270

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.44e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.221C>T (p.P74L) alteration is located in exon 1 (coding exon 1) of the TRMT44 gene. This alteration results from a C to T substitution at nucleotide position 221, causing the proline (P) at amino acid position 74 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.47

M_CAP

Benign

0.0037

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.4

REVEL

Benign

0.080

Sift

Uncertain

0.010

Sift4G

Benign

0.45

Vest4

0.12

MutPred

0.20

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.15

MPC

0.022

ClinPred

0.36

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over