rs6081268

Positions:

• chr20-18642516-A-G
• chr20-18642516-A-T

Variant summary

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

The NM_080820.6(DTD1):​c.477+14283A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,760 control chromosomes in the GnomAD database, including 20,055 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 0.51 (20055 hom., cov: 31)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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:):

DUXAP7 (HGNC:32186): (double homeobox A pseudogene 7) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This pseudogene is a member of the DUXA homeobox gene family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTD1	NM_080820.6	c.477+14283A>G		intron_variant		ENST00000377452.4	NP_543010.3
DUXAP7		n.18642516A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.477+14283A>G		intron_variant		1	NM_080820.6	ENSP00000366672.4
ENSG00000284776	ENST00000618693.4	c.552+14283A>G		intron_variant		5		ENSP00000482916.1
DTD1	ENST00000647441.1	n.*140+14283A>G		intron_variant				ENSP00000493969.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77282 AN: 151642 Hom.: 20047 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.509 AC: 77318 AN: 151760 Hom.: 20055 Cov.: 31 AF XY: 0.504 AC XY: 37349 AN XY: 74114

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.562

Alfa AF: 0.520 Hom.: 2513

Bravo AF: 0.507

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.58

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: rs6081268; hg19: chr20-18623160;