Variant chr13-94443547-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The NM_001922.5(DCT):c.1270A>G(p.Ile424Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

DCT
NM_001922.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.28

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38928074).

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000592 (9/152136) while in subpopulation EAS AF= 0.000965 (5/5184). AF 95% confidence interval is 0.00038. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCT	NM_001922.5 link	c.1270A>G	p.Ile424Val	missense_variant	7/8	ENST00000377028.10	NP_001913.2	P40126-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCT	ENST00000377028.10 link	c.1270A>G	p.Ile424Val	missense_variant	7/8	1	NM_001922.5	ENSP00000366227.4	P40126-1
DCT	ENST00000446125.1 link	c.1369A>G	p.Ile457Val	missense_variant	9/10	1		ENSP00000392762.1	P40126-2
DCT	ENST00000483392.6 link	n.*145A>G		non_coding_transcript_exon_variant	8/9	5		ENSP00000431275.2	A0A0A0MTD3
DCT	ENST00000483392.6 link	n.*145A>G		3_prime_UTR_variant	8/9	5		ENSP00000431275.2	A0A0A0MTD3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251142

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461648

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000331

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.1369A>G (p.I457V) alteration is located in exon 9 (coding exon 9) of the DCT gene. This alteration results from a A to G substitution at nucleotide position 1369, causing the isoleucine (I) at amino acid position 457 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.39

T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

2.9

M;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.73

N;N

REVEL

Uncertain

0.64

Sift

Uncertain

0.021

D;T

Sift4G

Uncertain

0.031

D;D

Polyphen

0.99

D;.

Vest4

0.50

MutPred

0.46

Loss of sheet (P = 0.0104);.;

MVP

0.92

MPC

0.26

ClinPred

0.70

GERP RS

5.9

Varity_R

0.19

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over