Variant chr3-69026027-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007114.3(TMF1):c.2828T>C(p.Met943Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M943R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TMF1
NM_007114.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

TMF1 (HGNC:11870): (TATA element modulatory factor 1) Enables androgen receptor binding activity and nuclear receptor coactivator activity. Involved in androgen receptor signaling pathway and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

TMF1 links:

EOGT-DT (HGNC:55605): (EOGT divergent transcript)

EOGT-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMF1	NM_007114.3 linkuse as main transcript	c.2828T>C	p.Met943Thr	missense_variant	14/17	ENST00000398559.7
TMF1	NM_001363879.1 linkuse as main transcript	c.2837T>C	p.Met946Thr	missense_variant	14/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMF1	ENST00000398559.7 linkuse as main transcript	c.2828T>C	p.Met943Thr	missense_variant	14/17	1	NM_007114.3	P4	P82094-1
EOGT-DT	ENST00000595925.1 linkuse as main transcript	n.38+11826A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249470

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000982

ExAC

AF:

0.0000165

AC:

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

Jun 22, 2024

The c.2828T>C (p.M943T) alteration is located in exon 14 (coding exon 14) of the TMF1 gene. This alteration results from a T to C substitution at nucleotide position 2828, causing the methionine (M) at amino acid position 943 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

0.078

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.021

T;.;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.060

N;.;.

REVEL

Benign

0.032

Sift

Benign

0.48

T;.;.

Sift4G

Benign

0.63

T;.;.

Polyphen

0.0

B;.;B

Vest4

0.36

MutPred

0.25

Gain of phosphorylation at M943 (P = 0.0373);.;.;

MVP

0.38

MPC

0.11

ClinPred

0.012

GERP RS

2.5

Varity_R

0.022

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 44

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