rs7096079

Positions:

• chr10-17138676-A-C

Variant summary

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

The NM_004412.7(TRDMT1):​c.*10364T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,030 control chromosomes in the GnomAD database, including 22,457 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 0.54 (22457 hom., cov: 32)
• Consequence: TRDMT1 NM_004412.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDMT1	NM_004412.7	c.*10364T>G		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.*10364T>G		3_prime_UTR_variant	11/11	1	NM_004412.7	ENSP00000367030	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82119 AN: 151912 Hom.: 22437 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.532

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82173 AN: 152030 Hom.: 22457 Cov.: 32 AF XY: 0.540 AC XY: 40117 AN XY: 74298

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.529

Alfa AF: 0.537 Hom.: 2733

Bravo AF: 0.532

Asia WGS AF: 0.538 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7096079; hg19: chr10-17180675;