10-17146475-C-T

Position:

• chr10-17146475-C-T

Variant summary

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

The ENST00000377799.8(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 ENST00000377799.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDMT1	NM_004412.7	c.*2565G>A		3_prime_UTR_variant	11/11	ENST00000377799.8	NP_004403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDMT1	ENST00000377799.8	c.*2565G>A		3_prime_UTR_variant	11/11	1	NM_004412.7	ENSP00000367030	P1
TRDMT1	ENST00000354631.7	c.*3761G>A		3_prime_UTR_variant, NMD_transcript_variant	12/12	1		ENSP00000346652

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

Gnomad4 AFR exome AF: 0.916

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.994

Gnomad4 EAS exome AF: 0.755

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.971

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.973

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

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.993

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.929

Gnomad4 FIN AF: 0.971

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.964

Alfa AF: 0.983 Hom.: 137304

Bravo AF: 0.935

Asia WGS AF: 0.877 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7074891; hg19: chr10-17188474;