rs6045524

Positions:

• chr20-18628986-T-A

Variant summary

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

The NM_080820.6(DTD1):​c.477+753T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 139,390 control chromosomes in the GnomAD database, including 19,329 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 0.53 (19329 hom., cov: 25)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTD1	NM_080820.6	c.477+753T>A		intron_variant		ENST00000377452.4
DTD1	NM_001318043.2	c.477+753T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTD1	ENST00000377452.4	c.477+753T>A		intron_variant		1	NM_080820.6	P1
DTD1	ENST00000494921.2	c.477+753T>A		intron_variant		2
DTD1	ENST00000647441.1	c.*140+753T>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.531 AC: 73957 AN: 139342 Hom.: 19321 Cov.: 25

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.591

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.531 AC: 73981 AN: 139390 Hom.: 19329 Cov.: 25 AF XY: 0.528 AC XY: 35109 AN XY: 66432

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.577

Alfa AF: 0.527 Hom.: 2623

Bravo AF: 0.509

Asia WGS AF: 0.344 AC: 1198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.53
DANN	Benign	0.89

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: rs6045524; hg19: chr20-18609630;