3-69026027-A-T

Variant names:

• chr3-69026027-A-T
• rs373885968
• NM_007114.3:c.2828T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007114.3(TMF1):​c.2828T>A​(p.Met943Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M943T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMF1 NM_007114.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51
• Publications: 0 publications found

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)

ACMG classification

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=0.07908973).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007114.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMF1	NM_007114.3	MANE Select	c.2828T>A	p.Met943Lys	missense	Exon 14 of 17	NP_009045.2	P82094-1
	TMF1	NM_001363879.1		c.2837T>A	p.Met946Lys	missense	Exon 14 of 17	NP_001350808.1	P82094-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMF1	ENST00000398559.7	TSL:1 MANE Select	c.2828T>A	p.Met943Lys	missense	Exon 14 of 17	ENSP00000381567.2	P82094-1
	TMF1	ENST00000948167.1		c.2843T>A	p.Met948Lys	missense	Exon 14 of 17	ENSP00000618226.1
	TMF1	ENST00000646708.1		c.2837T>A	p.Met946Lys	missense	Exon 14 of 17	ENSP00000494067.1	P82094-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461752 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111920

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.52	N
REVEL	Uncertain	0.30
Sift	Benign	0.39	T
Sift4G	Benign	0.93	T
Polyphen		0.057	B
Vest4		0.72
MutPred		0.30		Gain of ubiquitination at M943 (P = 0.0022)
MVP		0.42
MPC		0.16
ClinPred		0.15	T
GERP RS		2.5
Varity_R		0.086
gMVP		0.25
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373885968; hg19: chr3-69075178;