rs727299

Positions:

• chr13-94456247-C-T

Variant summary

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

The NM_001922.5(DCT):​c.1179+3844G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,186 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 0.085 (748 hom., cov: 32)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

Genes affected

DCT (HGNC:2709): (dopachrome tautomerase) Predicted to enable dopachrome isomerase activity. Involved in response to blue light. Located in intracellular membrane-bounded organelle and plasma membrane. Implicated in oculocutaneous albinism. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCT	NM_001922.5	c.1179+3844G>A		intron_variant		ENST00000377028.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCT	ENST00000377028.10	c.1179+3844G>A		intron_variant		1	NM_001922.5	P1
DCT	ENST00000446125.1	c.1180-3585G>A		intron_variant		1
DCT	ENST00000483392.6	c.609+3844G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12867 AN: 152068 Hom.: 747 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0846 AC: 12881 AN: 152186 Hom.: 748 Cov.: 32 AF XY: 0.0826 AC XY: 6149 AN XY: 74410

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.0603

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.0329

Gnomad4 NFE AF: 0.0541

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0626 Hom.: 202

Bravo AF: 0.0897

Asia WGS AF: 0.0240 AC: 85 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.65

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: rs727299; hg19: chr13-95108501;