rs12876569

Variant names:

• chr13-94466352-G-C
• rs12876569
• NM_001922.5:c.696+206C>G

Variant summary

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

The NM_001922.5(DCT):​c.696+206C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,822 control chromosomes in the GnomAD database, including 2,100 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 0.16 (2100 hom., cov: 30)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCT	NM_001922.5	c.696+206C>G		intron_variant	Intron 3 of 7	ENST00000377028.10	NP_001913.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCT	ENST00000377028.10	c.696+206C>G		intron_variant	Intron 3 of 7	1	NM_001922.5	ENSP00000366227.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24003 AN: 151704 Hom.: 2099 Cov.: 30

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00740

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.158 AC: 24011 AN: 151822 Hom.: 2100 Cov.: 30 AF XY: 0.157 AC XY: 11617 AN XY: 74172

African (AFR) AF: 0.113 AC: 4669 AN: 41416

American (AMR) AF: 0.122 AC: 1867 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3466

East Asian (EAS) AF: 0.00742 AC: 38 AN: 5120

South Asian (SAS) AF: 0.108 AC: 517 AN: 4808

European-Finnish (FIN) AF: 0.199 AC: 2088 AN: 10518

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.203 AC: 13766 AN: 67934

Other (OTH) AF: 0.139 AC: 292 AN: 2104

Alfa AF: 0.188 Hom.: 355

Bravo AF: 0.147

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		0.10
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: rs12876569; hg19: chr13-95118606;