chr20-18738545-A-G

Position:

• chr20-18738545-A-G

Variant summary

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

The ENST00000377452.4(DTD1):​c.478-5555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,062 control chromosomes in the GnomAD database, including 8,013 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 0.31 (8013 hom., cov: 32)
• Consequence: DTD1 ENST00000377452.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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 (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTD1	NM_080820.6	c.478-5555A>G		intron_variant		ENST00000377452.4	NP_543010.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.478-5555A>G		intron_variant		1	NM_080820.6	ENSP00000366672	P1
DTD1	ENST00000647441.1	c.*141-5555A>G		intron_variant, NMD_transcript_variant				ENSP00000493969

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47664 AN: 151944 Hom.: 8008 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.314 AC: 47673 AN: 152062 Hom.: 8013 Cov.: 32 AF XY: 0.307 AC XY: 22834 AN XY: 74314

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.352

Alfa AF: 0.342 Hom.: 1172

Bravo AF: 0.303

Asia WGS AF: 0.203 AC: 709 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	2.8
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: rs6081338; hg19: chr20-18719189;