7-115984315-G-A

Position:

chr7-115984315-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012252.4(TFEC):c.127C>T(p.Pro43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 0 hom. )

Consequence

TFEC
NM_012252.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

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:

TFEC (HGNC:):

TFEC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10238266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFEC	NM_012252.4 linkuse as main transcript	c.127C>T	p.Pro43Ser	missense_variant	2/8	ENST00000265440.12	NP_036384.1	O14948-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TFEC	ENST00000265440.12 linkuse as main transcript	c.127C>T	p.Pro43Ser	missense_variant	2/8	1	NM_012252.4	ENSP00000265440.7	O14948-1
TFEC	ENST00000320239.11 linkuse as main transcript	c.127C>T	p.Pro43Ser	missense_variant	2/7	1		ENSP00000318676.7	O14948-2
TFEC	ENST00000484212.5 linkuse as main transcript	c.397C>T	p.Pro133Ser	missense_variant	4/9	2		ENSP00000417432.1	B7Z757
TFEC	ENST00000393485.5 linkuse as main transcript	c.127C>T	p.Pro43Ser	missense_variant	2/6	2		ENSP00000377125.1	O14948-3

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251018

Hom.:

AF XY:

0.000435

AC XY:

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000750

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000752

AC:

1099

AN:

1461790

Hom.:

Cov.:

AF XY:

0.000718

AC XY:

522

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000932

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.000401

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000622

Hom.:

Bravo

AF:

0.000502

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000771

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

Jan 20, 2023

The c.127C>T (p.P43S) alteration is located in exon 2 (coding exon 1) of the TFEC gene. This alteration results from a C to T substitution at nucleotide position 127, causing the proline (P) at amino acid position 43 to be replaced by a serine (S). 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

0.078

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;.;.;.

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

L;L;L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.60

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.92

T;T;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.35

MVP

0.46

MPC

0.070

ClinPred

0.031

GERP RS

4.2

Varity_R

0.024

gMVP

0.37

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