chr11-61339420-G-C

Position:

• chr11-61339420-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015533.4(TKFC):​c.471G>C​(p.Thr157Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 1,611,142 control chromosomes in the GnomAD database, including 745,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (56165 hom., cov: 32)
  • Exomes 𝑓: 0.97 (689224 hom.)
• Consequence: TKFC NM_015533.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.65

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]

TKFC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-61339420-G-C is Benign according to our data. Variant chr11-61339420-G-C is described in ClinVar as [Benign]. Clinvar id is 1255450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TKFC	NM_015533.4	c.471G>C	p.Thr157Thr	synonymous_variant	5/18	ENST00000394900.8	NP_056348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TKFC	ENST00000394900.8	c.471G>C	p.Thr157Thr	synonymous_variant	5/18	1	NM_015533.4	ENSP00000378360.3
DDB1	ENST00000540166.5	n.-166+2948C>G		intron_variant		2		ENSP00000440269.1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124786 AN: 152076 Hom.: 56170 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.871

GnomAD3 exomes AF: 0.932 AC: 228448 AN: 245074 Hom.: 109131 AF XY: 0.939 AC XY: 125196 AN XY: 133356

Gnomad AFR exome AF: 0.398

Gnomad AMR exome AF: 0.969

Gnomad ASJ exome AF: 0.989

Gnomad EAS exome AF: 0.962

Gnomad SAS exome AF: 0.869

Gnomad FIN exome AF: 0.985

Gnomad NFE exome AF: 0.992

Gnomad OTH exome AF: 0.958

GnomAD4 exome AF: 0.967 AC: 1410974 AN: 1458948 Hom.: 689224 Cov.: 66 AF XY: 0.966 AC XY: 701161 AN XY: 725778

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.965

Gnomad4 ASJ exome AF: 0.988

Gnomad4 EAS exome AF: 0.960

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.985

Gnomad4 NFE exome AF: 0.992

Gnomad4 OTH exome AF: 0.938

GnomAD4 genome AF: 0.820 AC: 124792 AN: 152194 Hom.: 56165 Cov.: 32 AF XY: 0.822 AC XY: 61159 AN XY: 74418

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.933

Gnomad4 ASJ AF: 0.989

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.864

Alfa AF: 0.951 Hom.: 18287

Bravo AF: 0.803

Asia WGS AF: 0.839 AC: 2917 AN: 3478

EpiCase AF: 0.990

EpiControl AF: 0.991

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Triokinase and FMN cyclase deficiency syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.11
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2513329; hg19: chr11-61106892; COSMIC: COSV67523928; COSMIC: COSV67523928;