NM_001922.5:c.1180-220T>C

Variant names:

• chr13-94443857-A-G
• rs2296498
• NM_001922.5:c.1180-220T>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.1180-220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,138 control chromosomes in the GnomAD database, including 1,604 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 0.14 (1604 hom., cov: 32)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• 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)

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 (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCT	NM_001922.5	c.1180-220T>C		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.1180-220T>C		intron_variant	Intron 6 of 7	1	NM_001922.5	ENSP00000366227.4

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21207 AN: 152020 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.140 AC: 21238 AN: 152138 Hom.: 1604 Cov.: 32 AF XY: 0.139 AC XY: 10373 AN XY: 74380

African (AFR) AF: 0.177 AC: 7353 AN: 41492

American (AMR) AF: 0.139 AC: 2120 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3468

East Asian (EAS) AF: 0.0952 AC: 491 AN: 5160

South Asian (SAS) AF: 0.193 AC: 930 AN: 4820

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10586

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7981 AN: 68010

Other (OTH) AF: 0.147 AC: 310 AN: 2110

Alfa AF: 0.129 Hom.: 160

Bravo AF: 0.138

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.32
PhyloP100		-0.97
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: rs2296498; hg19: chr13-95096111;