Variant chr3-69026063-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007114.3(TMF1):c.2792C>T(p.Thr931Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,788 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: 0.0000021 ( 0 hom. )

Consequence

TMF1
NM_007114.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21656379).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMF1	NM_007114.3 linkuse as main transcript	c.2792C>T	p.Thr931Ile	missense_variant	14/17	ENST00000398559.7
TMF1	NM_001363879.1 linkuse as main transcript	c.2801C>T	p.Thr934Ile	missense_variant	14/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMF1	ENST00000398559.7 linkuse as main transcript	c.2792C>T	p.Thr931Ile	missense_variant	14/17	1	NM_007114.3	P4	P82094-1
EOGT-DT	ENST00000595925.1 linkuse as main transcript	n.38+11862G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249476

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000205

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

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

Oct 13, 2023

The c.2792C>T (p.T931I) alteration is located in exon 14 (coding exon 14) of the TMF1 gene. This alteration results from a C to T substitution at nucleotide position 2792, causing the threonine (T) at amino acid position 931 to be replaced by an isoleucine (I). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;D;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.0

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.6

D;.;.

REVEL

Benign

0.14

Sift

Uncertain

0.013

D;.;.

Sift4G

Benign

0.22

T;.;.

Polyphen

0.93

P;.;D

Vest4

0.30

MutPred

0.11

Loss of phosphorylation at T931 (P = 0.0126);.;.;

MVP

0.73

MPC

0.36

ClinPred

0.95

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.44

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