chr20-18726094-A-G

Position:

• chr20-18726094-A-G

Variant summary

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

The NM_080820.6(DTD1):​c.478-18006A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,222 control chromosomes in the GnomAD database, including 1,691 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 0.14 (1691 hom., cov: 33)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTD1	NM_080820.6	c.478-18006A>G		intron_variant		ENST00000377452.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTD1	ENST00000377452.4	c.478-18006A>G		intron_variant		1	NM_080820.6	P1
DTD1	ENST00000647441.1	c.*141-18006A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21909 AN: 152104 Hom.: 1693 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.144 AC: 21915 AN: 152222 Hom.: 1691 Cov.: 33 AF XY: 0.145 AC XY: 10762 AN XY: 74428

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.160

Alfa AF: 0.155 Hom.: 296

Bravo AF: 0.149

Asia WGS AF: 0.105 AC: 363 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	5.4
DANN	Benign	0.70

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: rs6132107; hg19: chr20-18706738;