rs6132093

Positions:

• chr20-18642697-C-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+14464C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,098 control chromosomes in the GnomAD database, including 19,973 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 (19934 hom., cov: 31)
  • Exomes 𝑓: 0.59 (39 hom.)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTD1	NM_080820.6	c.477+14464C>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+14464C>G		intron_variant		1	NM_080820.6	ENSP00000366672	P1
DTD1	ENST00000647441.1	c.*140+14464C>G		intron_variant, NMD_transcript_variant				ENSP00000493969

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77064 AN: 151758 Hom.: 19926 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.595 AC: 132 AN: 222 Hom.: 39 AF XY: 0.627 AC XY: 89 AN XY: 142

Gnomad4 AFR exome AF: 0.667

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.613

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.508 AC: 77100 AN: 151876 Hom.: 19934 Cov.: 31 AF XY: 0.502 AC XY: 37262 AN XY: 74230

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.558

Alfa AF: 0.526 Hom.: 2650

Bravo AF: 0.506

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.77

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: rs6132093; hg19: chr20-18623341;