11-61339053-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015533.4(TKFC):c.194-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 1,609,966 control chromosomes in the GnomAD database, including 730,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 55444 hom., cov: 33)

Exomes 𝑓: 0.96 ( 675422 hom. )

Consequence

TKFC
NM_015533.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.44

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

White-Kernohan syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

DDB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-61339053-C-T is Benign according to our data. Variant chr11-61339053-C-T is described in ClinVar as Benign. ClinVar VariationId is 1255449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015533.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TKFC	NM_015533.4	MANE Select	c.194-13C>T	intron	N/A	NP_056348.2
TKFC	NM_001351977.2		c.194-13C>T	intron	N/A	NP_001338906.1
TKFC	NM_001351976.2		c.194-13C>T	intron	N/A	NP_001338905.1	Q3LXA3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TKFC	ENST00000394900.8	TSL:1 MANE Select	c.194-13C>T	intron	N/A	ENSP00000378360.3	Q3LXA3-1
TKFC	ENST00000529479.5	TSL:1	c.191-13C>T	intron	N/A	ENSP00000432539.1	H0YCY6
DDB1	ENST00000540166.5	TSL:2	n.-166+3315G>A	intron	N/A	ENSP00000440269.1	F5GY55

Frequencies

GnomAD3 genomes

AF:

0.820

AC:

124703

AN:

152056

Hom.:

55452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.439

Gnomad AMI

AF:

0.966

Gnomad AMR

AF:

0.926

Gnomad ASJ

AF:

0.984

Gnomad EAS

AF:

0.963

Gnomad SAS

AF:

0.852

Gnomad FIN

AF:

0.964

Gnomad MID

AF:

0.915

Gnomad NFE

AF:

0.980

Gnomad OTH

AF:

0.865

GnomAD2 exomes

AF:

0.925

AC:

230563

AN:

249184

AF XY:

0.932

show subpopulations

Gnomad AFR exome

AF:

0.430

Gnomad AMR exome

AF:

0.965

Gnomad ASJ exome

AF:

0.984

Gnomad EAS exome

AF:

0.961

Gnomad FIN exome

AF:

0.965

Gnomad NFE exome

AF:

0.980

Gnomad OTH exome

AF:

0.948

GnomAD4 exome

AF:

0.958

AC:

1396994

AN:

1457792

Hom.:

675422

Cov.:

AF XY:

0.957

AC XY:

693876

AN XY:

724798

show subpopulations

African (AFR)

AF:

0.416

AC:

13905

AN:

33386

American (AMR)

AF:

0.961

AC:

42852

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.983

AC:

25541

AN:

25982

East Asian (EAS)

AF:

0.963

AC:

38174

AN:

39630

South Asian (SAS)

AF:

0.873

AC:

75059

AN:

85990

European-Finnish (FIN)

AF:

0.966

AC:

51322

AN:

53106

Middle Eastern (MID)

AF:

0.939

AC:

4732

AN:

5040

European-Non Finnish (NFE)

AF:

0.981

AC:

1089368

AN:

1109930

Other (OTH)

AF:

0.932

AC:

56041

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2566

5131

7697

10262

12828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21540

43080

64620

86160

107700

<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:

0.820

AC:

124709

AN:

152174

Hom.:

55444

Cov.:

AF XY:

0.821

AC XY:

61090

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.438

AC:

18185

AN:

41476

American (AMR)

AF:

0.926

AC:

14177

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.984

AC:

3418

AN:

3472

East Asian (EAS)

AF:

0.963

AC:

4980

AN:

5172

South Asian (SAS)

AF:

0.852

AC:

4117

AN:

4832

European-Finnish (FIN)

AF:

0.964

AC:

10236

AN:

10622

Middle Eastern (MID)

AF:

0.912

AC:

268

AN:

294

European-Non Finnish (NFE)

AF:

0.980

AC:

66636

AN:

67984

Other (OTH)

AF:

0.859

AC:

1811

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

712

1423

2135

2846

3558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.928

Hom.:

77078

Bravo

AF:

0.804

Asia WGS

AF:

0.838

AC:

2913

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Triokinase and FMN cyclase deficiency syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.015

(source)

DANN

Benign

0.59

PhyloP100

-2.4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over