chr13-94440642-T-C

Variant names:

• chr13-94440642-T-C
• rs3782974
• NM_001922.5:c.1382-566A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001922.5(DCT):​c.1382-566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 145,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000021 (0 hom., cov: 24)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• 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)

ENSG00000294700 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001922.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCT	NM_001922.5	MANE Select	c.1382-566A>G		intron	N/A	NP_001913.2
	DCT	NM_001129889.3		c.1481-566A>G		intron	N/A	NP_001123361.1
	DCT	NM_001322186.2		c.1193-566A>G		intron	N/A	NP_001309115.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCT	ENST00000377028.10	TSL:1 MANE Select	c.1382-566A>G		intron	N/A	ENSP00000366227.4
	DCT	ENST00000446125.1	TSL:1	c.1481-566A>G		intron	N/A	ENSP00000392762.1
	DCT	ENST00000483392.6	TSL:5	n.*257-566A>G		intron	N/A	ENSP00000431275.2

Frequencies

GnomAD3 genomes AF: 0.0000206 AC: 3 AN: 145938 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000769

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000206 AC: 3 AN: 145938 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 70550

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000769 AC: 3 AN: 39026

American (AMR) AF: 0.00 AC: 0 AN: 14368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67418

Other (OTH) AF: 0.00 AC: 0 AN: 2040

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1817

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.031
DANN	Benign	0.75
PhyloP100		-2.0

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: rs3782974; hg19: chr13-95092896;