13-94443759-T-C

Variant names:

• chr13-94443759-T-C
• rs1407995
• NM_001922.5:c.1180-122A>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.1180-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 723,948 control chromosomes in the GnomAD database, including 210,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.76 (45436 hom., cov: 31)
  • Exomes 𝑓: 0.75 (165516 hom.)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.633
• Publications: 13 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 (NFE) allele frequency at 95% confidence interval = 0.809 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.1180-122A>G		intron	N/A	NP_001913.2
	DCT	NM_001129889.3		c.1279-122A>G		intron	N/A	NP_001123361.1	P40126-2
	DCT	NM_001322186.2		c.991-122A>G		intron	N/A	NP_001309115.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCT	ENST00000377028.10	TSL:1 MANE Select	c.1180-122A>G		intron	N/A	ENSP00000366227.4	P40126-1
	DCT	ENST00000446125.1	TSL:1	c.1279-122A>G		intron	N/A	ENSP00000392762.1	P40126-2
	ENSG00000294700	ENST00000725276.1		n.259T>C		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116087 AN: 152008 Hom.: 45398 Cov.: 31

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.746 AC: 426733 AN: 571822 Hom.: 165516 AF XY: 0.744 AC XY: 223740 AN XY: 300864

African (AFR) AF: 0.799 AC: 12473 AN: 15608

American (AMR) AF: 0.538 AC: 15871 AN: 29510

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 12536 AN: 16502

East Asian (EAS) AF: 0.258 AC: 8244 AN: 31910

South Asian (SAS) AF: 0.647 AC: 34603 AN: 53448

European-Finnish (FIN) AF: 0.796 AC: 25332 AN: 31834

Middle Eastern (MID) AF: 0.759 AC: 1766 AN: 2328

European-Non Finnish (NFE) AF: 0.814 AC: 293198 AN: 360172

Other (OTH) AF: 0.744 AC: 22710 AN: 30510

GnomAD4 genome AF: 0.764 AC: 116170 AN: 152126 Hom.: 45436 Cov.: 31 AF XY: 0.755 AC XY: 56121 AN XY: 74348

African (AFR) AF: 0.795 AC: 32991 AN: 41508

American (AMR) AF: 0.641 AC: 9780 AN: 15268

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

East Asian (EAS) AF: 0.253 AC: 1307 AN: 5168

South Asian (SAS) AF: 0.647 AC: 3115 AN: 4818

European-Finnish (FIN) AF: 0.782 AC: 8271 AN: 10570

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55431 AN: 68002

Other (OTH) AF: 0.759 AC: 1606 AN: 2116

Alfa AF: 0.787 Hom.: 153582

Bravo AF: 0.747

Asia WGS AF: 0.501 AC: 1746 AN: 3476

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Age related macular degeneration 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.2
DANN	Benign	0.40
PhyloP100		0.63
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: rs1407995; hg19: chr13-95096013;