chr20-18643193-T-G

Position:

• chr20-18643193-T-G

Variant summary

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

The NM_080820.6(DTD1):​c.477+14960T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 240,516 control chromosomes in the GnomAD database, including 32,565 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 (20070 hom., cov: 32)
  • Exomes 𝑓: 0.52 (12495 hom.)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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]

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=-1.03).
• 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+14960T>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.477+14960T>G		intron_variant		1	NM_080820.6	ENSP00000366672	P1
DUXAP7	ENST00000431038.2	n.442A>C		non_coding_transcript_exon_variant	1/2
DTD1	ENST00000647441.1	c.*140+14960T>G		intron_variant, NMD_transcript_variant				ENSP00000493969

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77350 AN: 151906 Hom.: 20062 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.523 AC: 46289 AN: 88492 Hom.: 12495 Cov.: 0 AF XY: 0.518 AC XY: 25874 AN XY: 49944

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.670

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.509 AC: 77386 AN: 152024 Hom.: 20070 Cov.: 32 AF XY: 0.504 AC XY: 37427 AN XY: 74320

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.561

Alfa AF: 0.519 Hom.: 2510

Bravo AF: 0.507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.51

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: rs6132094; hg19: chr20-18623837;