20-18628925-T-G

Position:

• chr20-18628925-T-G

Variant summary

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

The ENST00000377452.4(DTD1):​c.477+692T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 150,708 control chromosomes in the GnomAD database, including 748 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 0.092 (748 hom., cov: 31)
• Consequence: DTD1 ENST00000377452.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTD1	NM_080820.6	c.477+692T>G		intron_variant		ENST00000377452.4	NP_543010.3
DTD1	NM_001318043.2	c.477+692T>G		intron_variant			NP_001304972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.477+692T>G		intron_variant		1	NM_080820.6	ENSP00000366672	P1
DTD1	ENST00000494921.2	c.477+692T>G		intron_variant		2		ENSP00000495845
DTD1	ENST00000647441.1	c.*140+692T>G		intron_variant, NMD_transcript_variant				ENSP00000493969

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13813 AN: 150640 Hom.: 747 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0891

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

GnomAD4 genome AF: 0.0916 AC: 13812 AN: 150708 Hom.: 748 Cov.: 31 AF XY: 0.0912 AC XY: 6698 AN XY: 73450

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0988

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0716

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.0378 Hom.: 33

Bravo AF: 0.0919

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.38

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: rs6136444; hg19: chr20-18609569;