Variant 4-99549376-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001134665.3(TRMT10A):c.752-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,609,248 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 175 hom. )

Consequence

TRMT10A
NM_001134665.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.488

Variant links:

Genes affected

TRMT10A (HGNC:28403): (tRNA methyltransferase 10A) This gene encodes a protein that belongs to the tRNA (Guanine-1)-methyltransferase family. A similar gene in yeast modifies several different tRNA species. Mutations in this gene are associated with microcephaly, short stature, and impaired glucose metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

TRMT10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 4-99549376-C-T is Benign according to our data. Variant chr4-99549376-C-T is described in ClinVar as [Benign]. Clinvar id is 1562217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT10A	NM_001134665.3 linkuse as main transcript	c.752-20G>A		intron_variant		ENST00000394876.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
TRMT10A	ENST00000394876.7 linkuse as main transcript	c.752-20G>A	intron_variant	1	NM_001134665.3	P1
TRMT10A	ENST00000273962.7 linkuse as main transcript	c.752-20G>A	intron_variant	1		P1
TRMT10A	ENST00000394877.7 linkuse as main transcript	c.752-20G>A	intron_variant	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

759

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0348

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.0152

AC:

3745

AN:

247018

Hom.:

136

AF XY:

0.0130

AC XY:

1735

AN XY:

133802

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.0731

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0290

Gnomad SAS exome

AF:

0.0206

Gnomad FIN exome

AF:

0.0000472

Gnomad NFE exome

AF:

0.000190

Gnomad OTH exome

AF:

0.00664

GnomAD4 exome

AF:

0.00401

AC:

5841

AN:

1456992

Hom.:

175

Cov.:

AF XY:

0.00414

AC XY:

2996

AN XY:

723992

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.0644

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.0225

Gnomad4 SAS exome

AF:

0.0195

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000159

Gnomad4 OTH exome

AF:

0.00352

GnomAD4 genome

AF:

0.00499

AC:

760

AN:

152256

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

450

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0349

Gnomad4 SAS

AF:

0.0256

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00768

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.3

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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