13-94448587-A-G

Variant names:

• chr13-94448587-A-G
• rs2031526
• NM_001922.5:c.1180-4950T>C

Variant summary

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

The NM_001922.5(DCT):​c.1180-4950T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,194 control chromosomes in the GnomAD database, including 49,865 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 (49865 hom., cov: 32)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• 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)

ENSG00000294700 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.907 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.1180-4950T>C		intron	N/A	NP_001913.2
	DCT	NM_001129889.3		c.1236-2826T>C		intron	N/A	NP_001123361.1
	DCT	NM_001322186.2		c.991-4950T>C		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.1180-4950T>C		intron	N/A	ENSP00000366227.4
	DCT	ENST00000446125.1	TSL:1	c.1236-2826T>C		intron	N/A	ENSP00000392762.1
	DCT	ENST00000483392.6	TSL:5	n.610-2826T>C		intron	N/A	ENSP00000431275.2

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121348 AN: 152076 Hom.: 49814 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.798 AC: 121453 AN: 152194 Hom.: 49865 Cov.: 32 AF XY: 0.789 AC XY: 58688 AN XY: 74400

African (AFR) AF: 0.915 AC: 38006 AN: 41554

American (AMR) AF: 0.653 AC: 9977 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2666 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5166

South Asian (SAS) AF: 0.646 AC: 3119 AN: 4828

European-Finnish (FIN) AF: 0.782 AC: 8274 AN: 10584

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

European-Non Finnish (NFE) AF: 0.816 AC: 55463 AN: 68002

Other (OTH) AF: 0.781 AC: 1644 AN: 2106

Alfa AF: 0.758 Hom.: 2348

Bravo AF: 0.785

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.52
PhyloP100		-0.039
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: rs2031526; hg19: chr13-95100841;