22-20113073-T-C

Variant names:

• chr22-20113073-T-C
• rs1633445
• NM_022727.6:c.1549+45A>G

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022727.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT2A	NM_022727.6	MANE Select	c.1549+45A>G		intron	N/A	NP_073564.3
	TRMT2A	NM_001331039.2		c.1603+45A>G		intron	N/A	NP_001317968.1	F2Z2W7
	TRMT2A	NM_182984.5		c.1549+45A>G		intron	N/A	NP_892029.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT2A	ENST00000252136.12	TSL:1 MANE Select	c.1549+45A>G		intron	N/A	ENSP00000252136.7	Q8IZ69-1
	TRMT2A	ENST00000403707.7	TSL:1	c.1549+45A>G		intron	N/A	ENSP00000385807.3	Q8IZ69-1
	TRMT2A	ENST00000439169.2	TSL:5	c.1603+45A>G		intron	N/A	ENSP00000395738.2	F2Z2W7

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

GnomAD2 exomes AF: 0.228 AC: 57105 AN: 250406 AF XY: 0.225

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 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

African (AFR) AF: 0.196 AC: 6556 AN: 33444

American (AMR) AF: 0.284 AC: 12675 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7824 AN: 26028

East Asian (EAS) AF: 0.219 AC: 8693 AN: 39652

South Asian (SAS) AF: 0.146 AC: 12543 AN: 86200

European-Finnish (FIN) AF: 0.241 AC: 12724 AN: 52716

Middle Eastern (MID) AF: 0.264 AC: 1521 AN: 5764

European-Non Finnish (NFE) AF: 0.240 AC: 266376 AN: 1109982

Other (OTH) AF: 0.237 AC: 14265 AN: 60306

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

African (AFR) AF: 0.195 AC: 8078 AN: 41514

American (AMR) AF: 0.263 AC: 4023 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1064 AN: 3472

East Asian (EAS) AF: 0.186 AC: 962 AN: 5178

South Asian (SAS) AF: 0.147 AC: 710 AN: 4828

European-Finnish (FIN) AF: 0.246 AC: 2608 AN: 10602

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16024 AN: 67986

Other (OTH) AF: 0.233 AC: 493 AN: 2114

Alfa AF: 0.233 Hom.: 16265

Bravo AF: 0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.62
PhyloP100		-0.077
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1633445; hg19: chr22-20100596; COSMIC: COSV52812309; COSMIC: COSV52812309;