rs6081270

Positions:

• chr20-18642975-G-A
• chr20-18642975-G-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+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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTD1	NM_080820.6	c.477+14742G>A		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+14742G>A		intron_variant		1	NM_080820.6	ENSP00000366672	P1
DUXAP7	ENST00000431038.2	n.500-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
DTD1	ENST00000647441.1	c.*140+14742G>A		intron_variant, NMD_transcript_variant				ENSP00000493969

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

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.348

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

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.278

Alfa AF: 0.346 Hom.: 1255

Bravo AF: 0.293

Asia WGS AF: 0.397 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.94
DANN	Benign	0.38

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: rs6081270; hg19: chr20-18623619;