rs6075382

Variant names:

• chr20-18642484-G-A
• rs6075382
• NM_080820.6:c.477+14251G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080820.6(DTD1):​c.477+14251G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,692 control chromosomes in the GnomAD database, including 16,819 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 0.46 (16819 hom., cov: 30)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTD1	NM_080820.6	c.477+14251G>A		intron_variant	Intron 4 of 5	ENST00000377452.4	NP_543010.3
DUXAP7		n.18642484G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.477+14251G>A		intron_variant	Intron 4 of 5	1	NM_080820.6	ENSP00000366672.4
ENSG00000284776	ENST00000618693.4	c.552+14251G>A		intron_variant	Intron 4 of 4	5		ENSP00000482916.1
DTD1	ENST00000647441.1	n.*140+14251G>A		intron_variant	Intron 5 of 6			ENSP00000493969.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70495 AN: 151574 Hom.: 16814 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.465 AC: 70520 AN: 151692 Hom.: 16819 Cov.: 30 AF XY: 0.460 AC XY: 34071 AN XY: 74090

African (AFR) AF: 0.385 AC: 15914 AN: 41368

American (AMR) AF: 0.479 AC: 7289 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2224 AN: 3464

East Asian (EAS) AF: 0.304 AC: 1569 AN: 5160

South Asian (SAS) AF: 0.356 AC: 1706 AN: 4786

European-Finnish (FIN) AF: 0.478 AC: 5016 AN: 10488

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35052 AN: 67926

Other (OTH) AF: 0.518 AC: 1081 AN: 2088

Alfa AF: 0.486 Hom.: 2358

Bravo AF: 0.461

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.4
DANN	Benign	0.88
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6075382; hg19: chr20-18623128;