rs6136423

Positions:

• chr20-18593603-G-A

Variant summary

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

The NM_080820.6(DTD1):​c.44-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 664,860 control chromosomes in the GnomAD database, including 7,222 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 0.14 (1715 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5507 hom.)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTD1	NM_080820.6	c.44-128G>A		intron_variant		ENST00000377452.4	NP_543010.3
DTD1	NM_001318043.2	c.44-128G>A		intron_variant			NP_001304972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.44-128G>A		intron_variant		1	NM_080820.6	ENSP00000366672	P1
DTD1	ENST00000494921.2	c.44-128G>A		intron_variant		2		ENSP00000495845
DTD1	ENST00000647441.1	c.44-128G>A		intron_variant, NMD_transcript_variant				ENSP00000493969

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22044 AN: 152016 Hom.: 1717 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.141 AC: 72206 AN: 512726 Hom.: 5507 AF XY: 0.136 AC XY: 37132 AN XY: 274034

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.0621

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.145 AC: 22050 AN: 152134 Hom.: 1715 Cov.: 32 AF XY: 0.146 AC XY: 10826 AN XY: 74378

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.0555

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.161

Alfa AF: 0.151 Hom.: 233

Bravo AF: 0.150

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.087
DANN	Benign	0.64

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: rs6136423; hg19: chr20-18574247;