Genetic Variant DCT:c.1180-122A>G (chr13-94443759-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.633

Publications

13 publications found

Variant links:

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)

DCT links:

ENSG00000294700 (HGNC:):

ENSG00000294700 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCT	NM_001922.5 link	c.1180-122A>G		intron_variant	Intron 6 of 7	ENST00000377028.10	NP_001913.2	P40126-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCT	ENST00000377028.10 link	c.1180-122A>G		intron_variant	Intron 6 of 7	1	NM_001922.5	ENSP00000366227.4		P40126-1

Frequencies

GnomAD3 genomes

AF:

0.764

AC:

116087

AN:

152008

Hom.:

45398

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4869

9739

14608

19478

24347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2582

5164

7746

10328

12910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.764

AC:

116170

AN:

152126

Hom.:

45436

Cov.:

AF XY:

0.755

AC XY:

56121

AN XY:

74348

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1321

2643

3964

5286

6607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.787

Hom.:

153582

Bravo

AF:

0.747

Asia WGS

AF:

0.501

AC:

1746

AN:

3476

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Age related macular degeneration 7

Other:1

School of Pharmacy, University of Eastern Finland

Significance:association

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.2

(source)

DANN

Benign

0.40

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over