10-12069091-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018706.7(DHTKD1):c.58T>C(p.Phe20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,612,620 control chromosomes in the GnomAD database, including 797,667 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.97 ( 71792 hom., cov: 35)

Exomes 𝑓: 1.0 ( 725875 hom. )

Consequence

DHTKD1
NM_018706.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.834

Variant links:

Genes affected

DHTKD1 (HGNC:23537): (dehydrogenase E1 and transketolase domain containing 1) This gene encodes a component of a mitochondrial 2-oxoglutarate-dehydrogenase-complex-like protein involved in the degradation pathways of several amino acids, including lysine. Mutations in this gene are associated with 2-aminoadipic 2-oxoadipic aciduria and Charcot-Marie-Tooth Disease Type 2Q. [provided by RefSeq, May 2013]

DHTKD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.919831E-7).

BP6

Variant 10-12069091-T-C is Benign according to our data. Variant chr10-12069091-T-C is described in ClinVar as [Benign]. Clinvar id is 1168371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-12069091-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHTKD1	NM_018706.7 link	c.58T>C	p.Phe20Leu	missense_variant	Exon 1 of 17	ENST00000263035.9	NP_061176.4	Q96HY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHTKD1	ENST00000263035.9 link	c.58T>C	p.Phe20Leu	missense_variant	Exon 1 of 17	1	NM_018706.7	ENSP00000263035.4		Q96HY7
DHTKD1	ENST00000437298.1 link	c.58T>C	p.Phe20Leu	missense_variant	Exon 1 of 5	3		ENSP00000388163.1		C9JWN1

Frequencies

GnomAD3 genomes

AF:

0.970

AC:

147589

AN:

152210

Hom.:

71740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.894

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.989

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.979

GnomAD3 exomes

AF:

0.992

AC:

242883

AN:

244766

Hom.:

120592

AF XY:

0.994

AC XY:

132939

AN XY:

133716

show subpopulations

Gnomad AFR exome

AF:

0.894

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.998

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.997

GnomAD4 exome

AF:

0.997

AC:

1455841

AN:

1460292

Hom.:

725875

Cov.:

AF XY:

0.997

AC XY:

724553

AN XY:

726448

show subpopulations

Gnomad4 AFR exome

AF:

0.895

Gnomad4 AMR exome

AF:

0.994

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.994

GnomAD4 genome

AF:

0.970

AC:

147700

AN:

152328

Hom.:

71792

Cov.:

AF XY:

0.972

AC XY:

72373

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.895

Gnomad4 AMR

AF:

0.989

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

0.999

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.980

Alfa

AF:

0.988

Hom.:

39433

Bravo

AF:

0.966

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.905

AC:

3965

ESP6500EA

AF:

0.999

AC:

8562

ExAC

AF:

0.990

AC:

119611

Asia WGS

AF:

0.996

AC:

3463

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

2-aminoadipic 2-oxoadipic aciduria

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease axonal type 2Q

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.7

DANN

Benign

0.56

DEOGEN2

Benign

0.000030

T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.23

T;T

MetaRNN

Benign

9.9e-7

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

N;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.062

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.014

MutPred

0.57

Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);

MPC

0.13

ClinPred

0.0021

GERP RS

-0.088

Varity_R

0.058

gMVP

0.34

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

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