10-17146475-C-T

Variant names:

• chr10-17146475-C-T
• rs7074891
• NM_004412.7:c.*2565G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004412.7(TRDMT1):​c.*2565G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 985,376 control chromosomes in the GnomAD database, including 480,023 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 0.95 (68783 hom., cov: 33)
  • Exomes 𝑓: 0.99 (411240 hom.)
• Consequence: TRDMT1 NM_004412.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 8 publications found

Genes affected

TRDMT1 (HGNC:2977): (tRNA aspartic acid methyltransferase 1) This gene encodes a protein responsible for the methylation of aspartic acid transfer RNA, specifically at the cytosine-38 residue in the anticodon loop. This enzyme also possesses residual DNA-(cytosine-C5) methyltransferase activity. While similar in sequence and structure to DNA cytosine methyltransferases, this gene is distinct and highly conserved in its function among taxa. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004412.7. 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
	TRDMT1	NM_004412.7	MANE Select	c.*2565G>A		3_prime_UTR	Exon 11 of 11	NP_004403.1	O14717-1
	TRDMT1	NM_001351219.2		c.*2565G>A		3_prime_UTR	Exon 11 of 11	NP_001338148.1
	TRDMT1	NM_001351221.2		c.*2565G>A		3_prime_UTR	Exon 9 of 9	NP_001338150.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDMT1	ENST00000377799.8	TSL:1 MANE Select	c.*2565G>A		3_prime_UTR	Exon 11 of 11	ENSP00000367030.3	O14717-1
	TRDMT1	ENST00000354631.7	TSL:1	n.*3761G>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000346652.3	Q7Z3E4
	TRDMT1	ENST00000354631.7	TSL:1	n.*3761G>A		3_prime_UTR	Exon 12 of 12	ENSP00000346652.3	Q7Z3E4

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144275 AN: 152168 Hom.: 68762 Cov.: 33

Gnomad AFR AF: 0.924

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.963

GnomAD4 exome AF: 0.993 AC: 827501 AN: 833090 Hom.: 411240 Cov.: 33 AF XY: 0.994 AC XY: 382203 AN XY: 384700

African (AFR) AF: 0.916 AC: 14454 AN: 15778

American (AMR) AF: 0.799 AC: 786 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 5119 AN: 5152

East Asian (EAS) AF: 0.755 AC: 2739 AN: 3630

South Asian (SAS) AF: 0.937 AC: 15418 AN: 16458

European-Finnish (FIN) AF: 0.971 AC: 268 AN: 276

Middle Eastern (MID) AF: 0.989 AC: 1602 AN: 1620

European-Non Finnish (NFE) AF: 0.998 AC: 760548 AN: 761896

Other (OTH) AF: 0.973 AC: 26567 AN: 27296

GnomAD4 genome AF: 0.948 AC: 144341 AN: 152286 Hom.: 68783 Cov.: 33 AF XY: 0.941 AC XY: 70103 AN XY: 74470

African (AFR) AF: 0.923 AC: 38353 AN: 41548

American (AMR) AF: 0.839 AC: 12820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3447 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3787 AN: 5164

South Asian (SAS) AF: 0.929 AC: 4485 AN: 4830

European-Finnish (FIN) AF: 0.971 AC: 10320 AN: 10628

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67894 AN: 68044

Other (OTH) AF: 0.964 AC: 2033 AN: 2110

Alfa AF: 0.976 Hom.: 215220

Bravo AF: 0.935

Asia WGS AF: 0.877 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
DANN	Benign	0.42
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7074891; hg19: chr10-17188474;