chr3-69029869-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007114.3(TMF1):​c.2540C>T​(p.Ala847Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A847T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMF1
NM_007114.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

Publications

0 publications found
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]
EOGT-DT (HGNC:55605): (EOGT divergent transcript)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08825794).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMF1NM_007114.3 linkc.2540C>T p.Ala847Val missense_variant Exon 11 of 17 ENST00000398559.7 NP_009045.2 P82094-1A0A024R370Q6PII6
TMF1NM_001363879.1 linkc.2549C>T p.Ala850Val missense_variant Exon 11 of 17 NP_001350808.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMF1ENST00000398559.7 linkc.2540C>T p.Ala847Val missense_variant Exon 11 of 17 1 NM_007114.3 ENSP00000381567.2 P82094-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461614
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727118
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33460
American (AMR)
AF:
0.00
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26120
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39678
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53374
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111870
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.2540C>T (p.A847V) alteration is located in exon 11 (coding exon 11) of the TMF1 gene. This alteration results from a C to T substitution at nucleotide position 2540, causing the alanine (A) at amino acid position 847 to be replaced by a valine (V). 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
0.080
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.11
T;.;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.77
T;T;T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.088
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
L;.;.
PhyloP100
2.9
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.7
N;.;.
REVEL
Benign
0.035
Sift
Benign
0.10
T;.;.
Sift4G
Uncertain
0.052
T;.;.
Polyphen
0.034
B;.;B
Vest4
0.30
MVP
0.54
MPC
0.10
ClinPred
0.35
T
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.043
gMVP
0.19
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs1046781265; hg19: chr3-69079020; API