NM_001922.5:c.1179+2240A>G

Variant names:

• chr13-94457851-T-C
• rs9301959
• NM_001922.5:c.1179+2240A>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.1179+2240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,910 control chromosomes in the GnomAD database, including 19,660 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 0.49 (19660 hom., cov: 31)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCT	NM_001922.5	c.1179+2240A>G		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.1179+2240A>G		intron_variant	Intron 6 of 7	1	NM_001922.5	ENSP00000366227.4
DCT	ENST00000446125.1	c.1179+2240A>G		intron_variant	Intron 6 of 9	1		ENSP00000392762.1
DCT	ENST00000483392.6	n.609+2240A>G		intron_variant	Intron 5 of 8	5		ENSP00000431275.2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74537 AN: 151792 Hom.: 19619 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.491 AC: 74635 AN: 151910 Hom.: 19660 Cov.: 31 AF XY: 0.485 AC XY: 36017 AN XY: 74234

African (AFR) AF: 0.668 AC: 27676 AN: 41430

American (AMR) AF: 0.382 AC: 5822 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1419 AN: 3468

East Asian (EAS) AF: 0.119 AC: 615 AN: 5166

South Asian (SAS) AF: 0.358 AC: 1722 AN: 4814

European-Finnish (FIN) AF: 0.462 AC: 4874 AN: 10542

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31076 AN: 67934

Other (OTH) AF: 0.444 AC: 936 AN: 2110

Alfa AF: 0.448 Hom.: 18970

Bravo AF: 0.486

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.27
PhyloP100		-0.65
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: rs9301959; hg19: chr13-95110105;