13-94443137-A-T

Variant names:

• chr13-94443137-A-T
• rs9524491
• NM_001922.5:c.1381+299T>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.1381+299T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,174 control chromosomes in the GnomAD database, including 50,341 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 0.80 (50341 hom., cov: 32)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

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.1381+299T>A		intron	N/A	NP_001913.2
	DCT	NM_001129889.3		c.1480+299T>A		intron	N/A	NP_001123361.1
	DCT	NM_001322186.2		c.1192+299T>A		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.1381+299T>A		intron	N/A	ENSP00000366227.4
	DCT	ENST00000446125.1	TSL:1	c.1480+299T>A		intron	N/A	ENSP00000392762.1
	DCT	ENST00000483392.6	TSL:5	n.*256+299T>A		intron	N/A	ENSP00000431275.2

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121865 AN: 152056 Hom.: 50286 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.802 AC: 121974 AN: 152174 Hom.: 50341 Cov.: 32 AF XY: 0.792 AC XY: 58942 AN XY: 74400

African (AFR) AF: 0.926 AC: 38450 AN: 41514

American (AMR) AF: 0.655 AC: 10013 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2667 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1311 AN: 5180

South Asian (SAS) AF: 0.646 AC: 3110 AN: 4812

European-Finnish (FIN) AF: 0.782 AC: 8282 AN: 10592

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55480 AN: 67998

Other (OTH) AF: 0.783 AC: 1656 AN: 2116

Alfa AF: 0.817 Hom.: 6382

Bravo AF: 0.790

Asia WGS AF: 0.510 AC: 1777 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.46
DANN	Benign	0.48
PhyloP100		-0.55
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: rs9524491; hg19: chr13-95095391;