13-94443759-T-C

Position:

• chr13-94443759-T-C

Variant summary

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

The NM_001922.5(DCT):​c.1180-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 723,948 control chromosomes in the GnomAD database, including 210,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.76 (45436 hom., cov: 31)
  • Exomes 𝑓: 0.75 (165516 hom.)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.633

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCT	NM_001922.5	c.1180-122A>G		intron_variant		ENST00000377028.10	NP_001913.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCT	ENST00000377028.10	c.1180-122A>G		intron_variant		1	NM_001922.5	ENSP00000366227.4
DCT	ENST00000446125.1	c.1279-122A>G		intron_variant		1		ENSP00000392762.1
DCT	ENST00000483392.6	n.*55-122A>G		intron_variant		5		ENSP00000431275.2

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116087 AN: 152008 Hom.: 45398 Cov.: 31

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.746 AC: 426733 AN: 571822 Hom.: 165516 AF XY: 0.744 AC XY: 223740 AN XY: 300864

Gnomad4 AFR exome AF: 0.799

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.760

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.814

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.764 AC: 116170 AN: 152126 Hom.: 45436 Cov.: 31 AF XY: 0.755 AC XY: 56121 AN XY: 74348

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.759

Alfa AF: 0.793 Hom.: 94922

Bravo AF: 0.747

Asia WGS AF: 0.501 AC: 1746 AN: 3476

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Age related macular degeneration 7 Other:1

association, no assertion criteria provided

research

School of Pharmacy, University of Eastern Finland

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.2
DANN	Benign	0.40

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: rs1407995; hg19: chr13-95096013;