11-61339053-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015533.4(TKFC):c.194-13C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1255449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TKFC	NM_015533.4	c.194-13C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000394900.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TKFC	ENST00000394900.8	c.194-13C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015533.4	P1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124703 AN: 152056 Hom.: 55452 Cov.: 33

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

GnomAD3 exomes AF: 0.925 AC: 230563 AN: 249184 Hom.: 109047 AF XY: 0.932 AC XY: 125646 AN XY: 134884

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 SAS exome AF: 0.868

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.: 37 AF XY: 0.957 AC XY: 693876 AN XY: 724798

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.961

Gnomad4 ASJ exome AF: 0.983

Gnomad4 EAS exome AF: 0.963

Gnomad4 SAS exome AF: 0.873

Gnomad4 FIN exome AF: 0.966

Gnomad4 NFE exome AF: 0.981

Gnomad4 OTH exome AF: 0.932

GnomAD4 genome AF: 0.820 AC: 124709 AN: 152174 Hom.: 55444 Cov.: 33 AF XY: 0.821 AC XY: 61090 AN XY: 74414

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.926

Gnomad4 ASJ AF: 0.984

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.980

Gnomad4 OTH AF: 0.859

Alfa AF: 0.950 Hom.: 61567

Bravo AF: 0.804

Asia WGS AF: 0.838 AC: 2913 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Triokinase and FMN cyclase deficiency syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.015
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs2512809; hg19: chr11-61106525;