13-94459405-C-T

Variant names:

• chr13-94459405-C-T
• rs9584234
• NM_001922.5:c.1179+686G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001922.5(DCT):​c.1179+686G>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 152,162 control chromosomes in the GnomAD database, including 1,643 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 (1643 hom., cov: 32)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459
• Publications: 4 publications found

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]

DCT Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 8

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCT	NM_001922.5	c.1179+686G>A		intron_variant	Intron 6 of 7	ENST00000377028.10	NP_001913.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCT	ENST00000377028.10	c.1179+686G>A		intron_variant	Intron 6 of 7	1	NM_001922.5	ENSP00000366227.4
DCT	ENST00000446125.1	c.1179+686G>A		intron_variant	Intron 6 of 9	1		ENSP00000392762.1
DCT	ENST00000483392.6	n.609+686G>A		intron_variant	Intron 5 of 8	5		ENSP00000431275.2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21571 AN: 152044 Hom.: 1642 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.142 AC: 21602 AN: 152162 Hom.: 1643 Cov.: 32 AF XY: 0.142 AC XY: 10553 AN XY: 74390

African (AFR) AF: 0.178 AC: 7403 AN: 41500

American (AMR) AF: 0.143 AC: 2184 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 560 AN: 3466

East Asian (EAS) AF: 0.111 AC: 576 AN: 5180

South Asian (SAS) AF: 0.196 AC: 945 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1442 AN: 10586

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8098 AN: 67990

Other (OTH) AF: 0.152 AC: 322 AN: 2112

Alfa AF: 0.127 Hom.: 4880

Bravo AF: 0.141

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.50
PhyloP100		0.46
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: rs9584234; hg19: chr13-95111659;