20-18709460-T-C

Variant names:

• chr20-18709460-T-C
• rs6035106
• NM_080820.6:c.478-34640T>C

Variant summary

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

The NM_080820.6(DTD1):​c.478-34640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,940 control chromosomes in the GnomAD database, including 16,714 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 0.46 (16714 hom., cov: 31)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 10 publications found

Genes affected

DTD1 (HGNC:16219): (D-aminoacyl-tRNA deacylase 1) The protein encoded by this gene is similar in sequence to histidyl-tRNA synthetase, which hydrolyzes D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr). The encoded protein binds the DNA unwinding element and plays a role in the initiation of DNA replication. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ENSG00000284776 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTD1	NM_080820.6	c.478-34640T>C		intron_variant	Intron 4 of 5	ENST00000377452.4	NP_543010.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.478-34640T>C		intron_variant	Intron 4 of 5	1	NM_080820.6	ENSP00000366672.4
ENSG00000284776	ENST00000618693.4	c.553-34640T>C		intron_variant	Intron 4 of 4	5		ENSP00000482916.1
DTD1	ENST00000647441.1	n.*141-34640T>C		intron_variant	Intron 5 of 6			ENSP00000493969.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69293 AN: 151822 Hom.: 16722 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.456 AC: 69298 AN: 151940 Hom.: 16714 Cov.: 31 AF XY: 0.461 AC XY: 34252 AN XY: 74260

African (AFR) AF: 0.295 AC: 12222 AN: 41442

American (AMR) AF: 0.494 AC: 7550 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3470

East Asian (EAS) AF: 0.584 AC: 2997 AN: 5130

South Asian (SAS) AF: 0.482 AC: 2318 AN: 4808

European-Finnish (FIN) AF: 0.574 AC: 6050 AN: 10532

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35319 AN: 67972

Other (OTH) AF: 0.437 AC: 920 AN: 2106

Alfa AF: 0.417 Hom.: 2343

Bravo AF: 0.444

Asia WGS AF: 0.496 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.55
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6035106; hg19: chr20-18690104;