chr13-94456247-C-T

Variant names:

• chr13-94456247-C-T
• rs727299
• NM_001922.5:c.1179+3844G>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+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
• Publications: 7 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=-0.87).
• 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 rank	MANE	Protein	UniProt
DCT	NM_001922.5	c.1179+3844G>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+3844G>A		intron_variant	Intron 6 of 7	1	NM_001922.5	ENSP00000366227.4
DCT	ENST00000446125.1	c.1180-3585G>A		intron_variant	Intron 6 of 9	1		ENSP00000392762.1
DCT	ENST00000483392.6	n.609+3844G>A		intron_variant	Intron 5 of 8	5		ENSP00000431275.2

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

African (AFR) AF: 0.177 AC: 7364 AN: 41498

American (AMR) AF: 0.0570 AC: 872 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0603 AC: 209 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0394 AC: 190 AN: 4822

European-Finnish (FIN) AF: 0.0329 AC: 349 AN: 10606

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0541 AC: 3680 AN: 68010

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0636 Hom.: 232

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
PhyloP100		-0.26
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: rs727299; hg19: chr13-95108501;