22-20113073-T-C

Position:

• chr22-20113073-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022727.6(TRMT2A):​c.1549+45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,610,972 control chromosomes in the GnomAD database, including 45,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4075 hom., cov: 33)
  • Exomes 𝑓: 0.24 (41251 hom.)
• Consequence: TRMT2A NM_022727.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

Genes affected

TRMT2A (HGNC:24974): (tRNA methyltransferase 2 homolog A) The protein encoded by this gene is of unknown function. However, it is orthologous to the mouse Trmt2a gene and contains an RNA methyltransferase domain. Expression of this gene varies during the cell cycle, with aberrant expression being a possible biomarker in certain breast cancers. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

TRMT2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT2A	NM_022727.6	c.1549+45A>G		intron_variant		ENST00000252136.12	NP_073564.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT2A	ENST00000252136.12	c.1549+45A>G		intron_variant		1	NM_022727.6	ENSP00000252136.7

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34269 AN: 152074 Hom.: 4075 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.237

GnomAD3 exomes AF: 0.228 AC: 57105 AN: 250406 Hom.: 6886 AF XY: 0.225 AC XY: 30433 AN XY: 135466

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.235 AC: 343177 AN: 1458780 Hom.: 41251 Cov.: 33 AF XY: 0.233 AC XY: 168804 AN XY: 725556

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.225 AC: 34287 AN: 152192 Hom.: 4075 Cov.: 33 AF XY: 0.226 AC XY: 16792 AN XY: 74406

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.233

Alfa AF: 0.235 Hom.: 7349

Bravo AF: 0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1633445; hg19: chr22-20100596; COSMIC: COSV52812309; COSMIC: COSV52812309;