20-18736085-C-T

Variant names:

• chr20-18736085-C-T
• rs4814783
• NM_080820.6:c.478-8015C>T

Variant summary

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

The ENST00000377452.4(DTD1):​c.478-8015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,046 control chromosomes in the GnomAD database, including 2,658 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 0.18 (2658 hom., cov: 32)
• Consequence: DTD1 ENST00000377452.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377452.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTD1	NM_080820.6	MANE Select	c.478-8015C>T		intron	N/A	NP_543010.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTD1	ENST00000377452.4	TSL:1 MANE Select	c.478-8015C>T		intron	N/A	ENSP00000366672.4
	ENSG00000284776	ENST00000618693.4	TSL:5	c.553-8015C>T		intron	N/A	ENSP00000482916.1
	DTD1	ENST00000647441.1		n.*141-8015C>T		intron	N/A	ENSP00000493969.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27284 AN: 151930 Hom.: 2662 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.179 AC: 27286 AN: 152046 Hom.: 2658 Cov.: 32 AF XY: 0.181 AC XY: 13425 AN XY: 74298

African (AFR) AF: 0.122 AC: 5082 AN: 41498

American (AMR) AF: 0.189 AC: 2883 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3466

East Asian (EAS) AF: 0.353 AC: 1824 AN: 5162

South Asian (SAS) AF: 0.253 AC: 1214 AN: 4800

European-Finnish (FIN) AF: 0.175 AC: 1847 AN: 10562

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.197 AC: 13369 AN: 67968

Other (OTH) AF: 0.167 AC: 352 AN: 2104

Alfa AF: 0.190 Hom.: 8017

Bravo AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.2
DANN	Benign	0.64
PhyloP100		-0.39
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: rs4814783; hg19: chr20-18716729; COSMIC: COSV66280290;