3-69023188-T-C

Variant names:

• chr3-69023188-T-C
• rs781080832
• NM_007114.3:c.3271A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007114.3(TMF1):​c.3271A>G​(p.Ser1091Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000497 in 1,610,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: TMF1 NM_007114.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043759286).

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.3271A>G	p.Ser1091Gly	missense	Exon 17 of 17	NP_009045.2	P82094-1
	TMF1	NM_001363879.1		c.3280A>G	p.Ser1094Gly	missense	Exon 17 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.3271A>G	p.Ser1091Gly	missense	Exon 17 of 17	ENSP00000381567.2	P82094-1
	TMF1	ENST00000948167.1		c.3286A>G	p.Ser1096Gly	missense	Exon 17 of 17	ENSP00000618226.1
	TMF1	ENST00000646708.1		c.3280A>G	p.Ser1094Gly	missense	Exon 17 of 17	ENSP00000494067.1	P82094-2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152080 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000243 AC: 6 AN: 247132 AF XY: 0.0000298

Gnomad AFR exome AF: 0.0000652

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000446

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000494 AC: 72 AN: 1458088 Hom.: 0 Cov.: 30 AF XY: 0.0000469 AC XY: 34 AN XY: 725418

African (AFR) AF: 0.00 AC: 0 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.00 AC: 0 AN: 85870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5670

European-Non Finnish (NFE) AF: 0.0000622 AC: 69 AN: 1109818

Other (OTH) AF: 0.0000332 AC: 2 AN: 60188

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152080 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67914

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000497 AC: 6

EpiCase AF: 0.0000547

EpiControl AF: 0.0000596

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.078
Sift	Benign	0.088	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.19		Loss of phosphorylation at S1091 (P = 0.0119)
MVP		0.26
MPC		0.096
ClinPred		0.019	T
GERP RS		3.1
Varity_R		0.057
gMVP		0.13
Mutation Taster		=94/6	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

Other links and lift over

dbSNP: rs781080832; hg19: chr3-69072339;