rs1006771

Positions:

• chr22-23971817-G-T

Variant summary

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

The NM_001084393.2(DDTL):​c.*411G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 600,156 control chromosomes in the GnomAD database, including 130,583 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 0.67 (33832 hom., cov: 32)
  • Exomes 𝑓: 0.65 (96751 hom.)
• Consequence: DDTL NM_001084393.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

DDTL (HGNC:33446): (D-dopachrome tautomerase like) Predicted to enable lyase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DDT (HGNC:2732): (D-dopachrome tautomerase) D-dopachrome tautomerase converts D-dopachrome into 5,6-dihydroxyindole. The DDT gene is related to the migration inhibitory factor (MIF) in terms of sequence, enzyme activity, and gene structure. DDT and MIF are closely linked on chromosome 22. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDTL	NM_001084393.2	c.*411G>T		3_prime_UTR_variant	3/3	ENST00000215770.6
DDT	NM_001084392.3	c.285-194C>A		intron_variant		ENST00000398344.9
DDT	NM_001355.4	c.285-194C>A		intron_variant
DDT	NM_001397485.1	c.285-194C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDTL	ENST00000215770.6	c.*411G>T		3_prime_UTR_variant	3/3	2	NM_001084393.2	P1
DDT	ENST00000398344.9	c.285-194C>A		intron_variant		1	NM_001084392.3	P1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101132 AN: 151378 Hom.: 33811 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.654 AC: 293462 AN: 448662 Hom.: 96751 Cov.: 4 AF XY: 0.657 AC XY: 155192 AN XY: 236090

Gnomad4 AFR exome AF: 0.701

Gnomad4 AMR exome AF: 0.637

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.702

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.668 AC: 101203 AN: 151494 Hom.: 33832 Cov.: 32 AF XY: 0.673 AC XY: 49777 AN XY: 73972

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.655

Alfa AF: 0.657 Hom.: 40128

Bravo AF: 0.661

Asia WGS AF: 0.661 AC: 2295 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.51

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: rs1006771; hg19: chr22-24314006; COSMIC: COSV53159760; COSMIC: COSV53159760;