Genetic Variant TRMT61A:p.Ser19Leu (chr14-103530034-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_152307.3(TRMT61A):c.56C>T(p.Ser19Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Consequence

TRMT61A
NM_152307.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

Variant links:

Genes affected

TRMT61A (HGNC:23790): (tRNA methyltransferase 61A) Enables mRNA (adenine-N1-)-methyltransferase activity. Involved in mRNA methylation. Predicted to be located in nucleoplasm. Predicted to be part of tRNA (m1A) methyltransferase complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TRMT61A 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=0.16014671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT61A	NM_152307.3 link	c.56C>T	p.Ser19Leu	missense_variant	Exon 2 of 4	ENST00000389749.9	NP_689520.2	Q96FX7A0A024R6Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT61A	ENST00000389749.9 link	c.56C>T	p.Ser19Leu	missense_variant	Exon 2 of 4	1	NM_152307.3	ENSP00000374399.4		Q96FX7
TRMT61A	ENST00000299202.4 link	c.34+773C>T		intron_variant	Intron 1 of 2	1		ENSP00000299202.4		H0Y2Q1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248312

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134938

show subpopulations

Gnomad AFR exome

AF:

0.0000637

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56C>T (p.S19L) alteration is located in exon 2 (coding exon 1) of the TRMT61A gene. This alteration results from a C to T substitution at nucleotide position 56, causing the serine (S) at amino acid position 19 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

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.46

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.012

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.55

REVEL

Benign

0.11

Sift

Uncertain

0.023

Sift4G

Uncertain

0.018

Polyphen

0.034

Vest4

0.34

MutPred

0.55

Gain of catalytic residue at H22 (P = 0.0017);

MVP

0.28

MPC

0.48

ClinPred

0.22

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.21

gMVP

0.79

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