20-18628925-T-G

Variant names:

• chr20-18628925-T-G
• rs6136444
• NM_080820.6:c.477+692T>G

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+692T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 150,708 control chromosomes in the GnomAD database, including 748 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 0.092 (748 hom., cov: 31)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 1 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 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+692T>G		intron	N/A	NP_543010.3
	DTD1	NM_001318043.2		c.477+692T>G		intron	N/A	NP_001304972.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTD1	ENST00000377452.4	TSL:1 MANE Select	c.477+692T>G		intron	N/A	ENSP00000366672.4
	ENSG00000284776	ENST00000618693.4	TSL:5	c.552+692T>G		intron	N/A	ENSP00000482916.1
	DTD1	ENST00000494921.2	TSL:2	c.477+692T>G		intron	N/A	ENSP00000495845.1

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13813 AN: 150640 Hom.: 747 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0891

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

GnomAD4 genome AF: 0.0916 AC: 13812 AN: 150708 Hom.: 748 Cov.: 31 AF XY: 0.0912 AC XY: 6698 AN XY: 73450

African (AFR) AF: 0.135 AC: 5509 AN: 40898

American (AMR) AF: 0.0643 AC: 970 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3460

East Asian (EAS) AF: 0.0988 AC: 505 AN: 5112

South Asian (SAS) AF: 0.141 AC: 673 AN: 4778

European-Finnish (FIN) AF: 0.0535 AC: 545 AN: 10196

Middle Eastern (MID) AF: 0.121 AC: 35 AN: 290

European-Non Finnish (NFE) AF: 0.0716 AC: 4860 AN: 67888

Other (OTH) AF: 0.0884 AC: 184 AN: 2082

Alfa AF: 0.0596 Hom.: 109

Bravo AF: 0.0919

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.38
PhyloP100		-0.16
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: rs6136444; hg19: chr20-18609569;