rs10490960

Positions:

• chr10-17178945-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004412.7(TRDMT1):​c.65-4285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 152,134 control chromosomes in the GnomAD database, including 11 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 0.0042 (11 hom., cov: 32)
• Consequence: TRDMT1 NM_004412.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502

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=-0.91).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00421 (640/152134) while in subpopulation SAS AF= 0.0199 (96/4818). AF 95% confidence interval is 0.0167. There are 11 homozygotes in gnomad4. There are 311 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRDMT1	NM_004412.7	c.65-4285A>G		intron_variant		ENST00000377799.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRDMT1	ENST00000377799.8	c.65-4285A>G		intron_variant		1	NM_004412.7	P1

Frequencies

GnomAD3 genomes AF: 0.00418 AC: 636 AN: 152014 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00262

Gnomad OTH AF: 0.00669

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

GnomAD4 genome AF: 0.00421 AC: 640 AN: 152134 Hom.: 11 Cov.: 32 AF XY: 0.00418 AC XY: 311 AN XY: 74382

Gnomad4 AFR AF: 0.000386

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00262

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00349 Hom.: 1

Bravo AF: 0.00462

Asia WGS AF: 0.00607 AC: 21 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs10490960; hg19: chr10-17220944;