4-99549376-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.488

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	c.752-20G>A		intron_variant		ENST00000394876.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT10A	ENST00000394876.7	c.752-20G>A		intron_variant		1	NM_001134665.3	P1
TRMT10A	ENST00000273962.7	c.752-20G>A		intron_variant		1		P1
TRMT10A	ENST00000394877.7	c.752-20G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.00499 AC: 759 AN: 152138 Hom.: 11 Cov.: 32

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

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.: 31 AF XY: 0.00414 AC XY: 2996 AN XY: 723992

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.: 11 Cov.: 32 AF XY: 0.00604 AC XY: 450 AN XY: 74452

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.: 0

Bravo AF: 0.00768

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

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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

Other links and lift over

dbSNP: rs80053092; hg19: chr4-100470533; COSMIC: COSV56745107; COSMIC: COSV56745107;