NM_001922.5:c.*1460A>T

Variant names:

• chr13-94438438-T-A
• rs1540979
• NM_001922.5:c.*1460A>T

Variant summary

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

The NM_001922.5(DCT):​c.*1460A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 288,804 control chromosomes in the GnomAD database, including 100,356 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 0.84 (54770 hom., cov: 32)
  • Exomes 𝑓: 0.80 (45586 hom.)
• Consequence: DCT NM_001922.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCT	NM_001922.5	MANE Select	c.*1460A>T		3_prime_UTR	Exon 8 of 8	NP_001913.2
	DCT	NM_001129889.3		c.*1460A>T		3_prime_UTR	Exon 10 of 10	NP_001123361.1
	DCT	NM_001322186.2		c.*1460A>T		3_prime_UTR	Exon 10 of 10	NP_001309115.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCT	ENST00000377028.10	TSL:1 MANE Select	c.*1460A>T		3_prime_UTR	Exon 8 of 8	ENSP00000366227.4
	ENSG00000294700	ENST00000725275.1		n.303+4780T>A		intron	N/A
	ENSG00000294700	ENST00000725276.1		n.241+4780T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127319 AN: 152052 Hom.: 54718 Cov.: 32

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.827

GnomAD4 exome AF: 0.805 AC: 109934 AN: 136636 Hom.: 45586 Cov.: 0 AF XY: 0.793 AC XY: 60433 AN XY: 76172

African (AFR) AF: 0.946 AC: 3213 AN: 3396

American (AMR) AF: 0.622 AC: 4133 AN: 6640

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 2626 AN: 2990

East Asian (EAS) AF: 0.299 AC: 1521 AN: 5086

South Asian (SAS) AF: 0.713 AC: 18899 AN: 26488

European-Finnish (FIN) AF: 0.865 AC: 5551 AN: 6418

Middle Eastern (MID) AF: 0.823 AC: 1395 AN: 1696

European-Non Finnish (NFE) AF: 0.870 AC: 67002 AN: 77034

Other (OTH) AF: 0.812 AC: 5594 AN: 6888

GnomAD4 genome AF: 0.837 AC: 127426 AN: 152168 Hom.: 54770 Cov.: 32 AF XY: 0.830 AC XY: 61726 AN XY: 74380

African (AFR) AF: 0.939 AC: 38996 AN: 41516

American (AMR) AF: 0.677 AC: 10342 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3039 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1469 AN: 5162

South Asian (SAS) AF: 0.696 AC: 3350 AN: 4816

European-Finnish (FIN) AF: 0.854 AC: 9055 AN: 10604

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58342 AN: 67998

Other (OTH) AF: 0.827 AC: 1748 AN: 2114

Alfa AF: 0.817 Hom.: 2619

Bravo AF: 0.821

Asia WGS AF: 0.550 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.76
PhyloP100		-1.0
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: rs1540979; hg19: chr13-95090692;