Variant 11-61339420-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015533.4(TKFC):c.471G>C(p.Thr157=) 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.65

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
TKFC	NM_015533.4 linkuse as main transcript	c.471G>C	p.Thr157=	synonymous_variant	5/18	ENST00000394900.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TKFC	ENST00000394900.8 linkuse as main transcript	c.471G>C	p.Thr157=	synonymous_variant	5/18	1	NM_015533.4	P1	Q3LXA3-1

Frequencies

GnomAD3 genomes

AF:

0.821

AC:

124786

AN:

152076

Hom.:

56170

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.966

AC XY:

701161

AN XY:

725778

show subpopulations

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.:

AF XY:

0.822

AC XY:

61159

AN XY:

74418

show subpopulations

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Triokinase and FMN cyclase deficiency syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

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