chr20-18642975-G-A

Variant names:

• chr20-18642975-G-A
• rs6081270
• NM_080820.6:c.477+14742G>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+14742G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,896 control chromosomes in the GnomAD database, including 8,295 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 0.31 (8207 hom., cov: 30)
  • Exomes 𝑓: 0.36 (88 hom.)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080820.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTD1	NM_080820.6	MANE Select	c.477+14742G>A		intron	N/A	NP_543010.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTD1	ENST00000377452.4	TSL:1 MANE Select	c.477+14742G>A		intron	N/A	ENSP00000366672.4
	ENSG00000284776	ENST00000618693.4	TSL:5	c.552+14742G>A		intron	N/A	ENSP00000482916.1
	DUXAP7	ENST00000431038.2	TSL:6	n.500-4C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47312 AN: 150646 Hom.: 8213 Cov.: 30

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.365 AC: 416 AN: 1140 Hom.: 88 Cov.: 0 AF XY: 0.346 AC XY: 233 AN XY: 674

African (AFR) AF: 0.250 AC: 3 AN: 12

American (AMR) AF: 0.125 AC: 2 AN: 16

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6 AN: 24

East Asian (EAS) AF: 0.292 AC: 7 AN: 24

South Asian (SAS) AF: 0.399 AC: 55 AN: 138

European-Finnish (FIN) AF: 0.452 AC: 28 AN: 62

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.367 AC: 299 AN: 814

Other (OTH) AF: 0.348 AC: 16 AN: 46

GnomAD4 genome AF: 0.314 AC: 47313 AN: 150756 Hom.: 8207 Cov.: 30 AF XY: 0.319 AC XY: 23469 AN XY: 73532

African (AFR) AF: 0.170 AC: 6961 AN: 40990

American (AMR) AF: 0.298 AC: 4511 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 750 AN: 3462

East Asian (EAS) AF: 0.422 AC: 2156 AN: 5112

South Asian (SAS) AF: 0.429 AC: 2050 AN: 4784

European-Finnish (FIN) AF: 0.423 AC: 4328 AN: 10238

Middle Eastern (MID) AF: 0.302 AC: 87 AN: 288

European-Non Finnish (NFE) AF: 0.378 AC: 25605 AN: 67774

Other (OTH) AF: 0.278 AC: 579 AN: 2082

Alfa AF: 0.339 Hom.: 1264

Bravo AF: 0.293

Asia WGS AF: 0.397 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.94
DANN	Benign	0.38
PhyloP100		0.52
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: rs6081270; hg19: chr20-18623619;