chr11-61339293-G-A

Position:

chr11-61339293-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015533.4(TKFC):c.344G>A(p.Arg115Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,613,852 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0041 ( 21 hom. )

Consequence

TKFC
NM_015533.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.85

Variant links:

Genes affected

TKFC (HGNC:24552): (triokinase and FMN cyclase) This gene is a member of the family of dihydroxyacetone kinases, which have a protein structure distinct from other kinases. The product of this gene phosphorylates dihydroxyacetone, and also catalyzes the formation of riboflavin 4',5'-phosphate (aka cyclin FMN) from FAD. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2017]

TKFC links:

DDB1 (HGNC:2717): (damage specific DNA binding protein 1) The protein encoded by this gene is the large subunit (p127) of the heterodimeric DNA damage-binding (DDB) complex while another protein (p48) forms the small subunit. This protein complex functions in nucleotide-excision repair and binds to DNA following UV damage. Defective activity of this complex causes the repair defect in patients with xeroderma pigmentosum complementation group E (XPE) - an autosomal recessive disorder characterized by photosensitivity and early onset of carcinomas. However, it remains for mutation analysis to demonstrate whether the defect in XPE patients is in this gene or the gene encoding the small subunit. In addition, Best vitelliform mascular dystrophy is mapped to the same region as this gene on 11q, but no sequence alternations of this gene are demonstrated in Best disease patients. The protein encoded by this gene also functions as an adaptor molecule for the cullin 4 (CUL4) ubiquitin E3 ligase complex by facilitating the binding of substrates to this complex and the ubiquitination of proteins. [provided by RefSeq, May 2012]

DDB1 links:

TKFC (HGNC:):

TKFC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025957704).

BP6

Variant 11-61339293-G-A is Benign according to our data. Variant chr11-61339293-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2578659.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TKFC	NM_015533.4 linkuse as main transcript	c.344G>A	p.Arg115Gln	missense_variant	5/18	ENST00000394900.8	NP_056348.2	Q3LXA3-1A0A140VJH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TKFC	ENST00000394900.8 linkuse as main transcript	c.344G>A	p.Arg115Gln	missense_variant	5/18	1	NM_015533.4	ENSP00000378360.3		Q3LXA3-1
DDB1	ENST00000540166.5 linkuse as main transcript	n.-166+3075C>T		intron_variant		2		ENSP00000440269.1		F5GY55

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

442

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00454

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00252

AC:

631

AN:

250624

Hom.:

AF XY:

0.00245

AC XY:

332

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.000985

Gnomad ASJ exome

AF:

0.000598

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.00278

Gnomad NFE exome

AF:

0.00376

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00407

AC:

5947

AN:

1461486

Hom.:

Cov.:

AF XY:

0.00401

AC XY:

2919

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.00333

Gnomad4 NFE exome

AF:

0.00476

Gnomad4 OTH exome

AF:

0.00349

GnomAD4 genome

AF:

0.00290

AC:

442

AN:

152366

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

203

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00263

Gnomad4 NFE

AF:

0.00454

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.00264

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00240

AC:

291

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00273

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

TKFC: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

T;T;.

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.067

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.54

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;T;D

Polyphen

1.0

D;.;.

Vest4

0.89

MVP

0.60

MPC

0.67

ClinPred

0.083

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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