Variant chr13-94443596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_001922.5(DCT):c.1221G>A(p.Met407Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,461,656 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: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

DCT
NM_001922.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000157 (23/1461656) while in subpopulation EAS AF= 0.000529 (21/39674). AF 95% confidence interval is 0.000355. There are 0 homozygotes in gnomad4_exome. There are 12 alleles in male gnomad4_exome subpopulation. Median coverage is 32. 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	UniProt
DCT	NM_001922.5 linkuse as main transcript	c.1221G>A	p.Met407Ile	missense_variant	7/8	ENST00000377028.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCT	ENST00000377028.10 linkuse as main transcript	c.1221G>A	p.Met407Ile	missense_variant	7/8	1	NM_001922.5	P1	P40126-1
DCT	ENST00000446125.1 linkuse as main transcript	c.1320G>A	p.Met440Ile	missense_variant	9/10	1			P40126-2
DCT	ENST00000483392.6 linkuse as main transcript	c.*96G>A		3_prime_UTR_variant, NMD_transcript_variant	8/9	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250850

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000824

AC:

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

Jul 19, 2023

The c.1320G>A (p.M440I) alteration is located in exon 9 (coding exon 9) of the DCT gene. This alteration results from a G to A substitution at nucleotide position 1320, causing the methionine (M) at amino acid position 440 to be replaced by an isoleucine (I). 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

Uncertain

0.51

BayesDel_addAF

Benign

0.00084

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.76

D;.

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;D

M_CAP

Benign

0.078

MetaRNN

Benign

0.30

T;T

MetaSVM

Pathogenic

0.81

MutationAssessor

Benign

0.87

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.0

N;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.018

D;T

Sift4G

Benign

0.075

T;T

Polyphen

0.016

B;.

Vest4

0.41

MutPred

0.60

Gain of methylation at K408 (P = 0.0253);.;

MVP

0.82

MPC

0.040

ClinPred

0.19

GERP RS

5.8

Varity_R

0.37

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -23

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