rs6136469

Positions:

• chr20-18681060-T-C

Variant summary

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

The NM_080820.6(DTD1):​c.477+52827T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,116 control chromosomes in the GnomAD database, including 9,513 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 0.34 (9513 hom., cov: 32)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTD1	NM_080820.6	c.477+52827T>C		intron_variant		ENST00000377452.4	NP_543010.3
DTD1-AS1	NR_109955.1	n.310-2081A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.477+52827T>C		intron_variant		1	NM_080820.6	ENSP00000366672.4
ENSG00000284776	ENST00000618693.4	c.552+52827T>C		intron_variant		5		ENSP00000482916.1
DTD1-AS1	ENST00000428285.1	n.311-2081A>G		intron_variant		1
DTD1	ENST00000647441.1	n.*140+52827T>C		intron_variant				ENSP00000493969.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52444 AN: 151996 Hom.: 9506 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.345 AC: 52474 AN: 152116 Hom.: 9513 Cov.: 32 AF XY: 0.339 AC XY: 25170 AN XY: 74356

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.381

Alfa AF: 0.397 Hom.: 24878

Bravo AF: 0.336

Asia WGS AF: 0.213 AC: 743 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.20

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: rs6136469; hg19: chr20-18661704;