Variant 7-115942035-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012252.4(TFEC):c.521T>C(p.Met174Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TFEC
NM_012252.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

Variant links:

Genes affected

TFEC (HGNC:11754): (transcription factor EC) This gene encodes a member of the micropthalmia (MiT) family of basic helix-loop-helix leucine zipper transcription factors. MiT transcription factors regulate the expression of target genes by binding to E-box recognition sequences as homo- or heterodimers, and play roles in multiple cellular processes including survival, growth and differentiation. The encoded protein is a transcriptional activator of the nonmuscle myosin II heavy chain-A gene, and may also co-regulate target genes in osteoclasts as a heterodimer with micropthalmia-associated transcription factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

TFEC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32717973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFEC	NM_012252.4 linkuse as main transcript	c.521T>C	p.Met174Thr	missense_variant	7/8	ENST00000265440.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFEC	ENST00000265440.12 linkuse as main transcript	c.521T>C	p.Met174Thr	missense_variant	7/8	1	NM_012252.4	P4	O14948-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459766

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.521T>C (p.M174T) alteration is located in exon 7 (coding exon 6) of the TFEC gene. This alteration results from a T to C substitution at nucleotide position 521, causing the methionine (M) at amino acid position 174 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Pathogenic

0.84

.;D;.;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.73

T;T;T;T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.33

T;T;T;T;T

MetaSVM

Uncertain

0.15

MutationAssessor

Benign

-0.30

.;N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-4.2

D;D;D;D;D

REVEL

Uncertain

0.42

Sift

Benign

0.094

T;T;T;T;D

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.0090, 0.0040, 0.027, 0.28

.;B;B;B;B

Vest4

0.45

MutPred

0.62

.;Gain of phosphorylation at M174 (P = 0.0519);.;.;.;

MVP

0.78

MPC

0.045

ClinPred

0.90

GERP RS

3.2

Varity_R

0.56

gMVP

0.60

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over