3-69024152-C-T

Variant names:

• chr3-69024152-C-T
• rs1485121884
• NM_007114.3:c.3041G>A

Variant summary

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

The NM_007114.3(TMF1):​c.3041G>A​(p.Arg1014Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,453,926 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TMF1 NM_007114.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

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

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 rank	MANE	Protein	UniProt
TMF1	NM_007114.3	c.3041G>A	p.Arg1014Gln	missense_variant	Exon 16 of 17	ENST00000398559.7	NP_009045.2
TMF1	NM_001363879.1	c.3050G>A	p.Arg1017Gln	missense_variant	Exon 16 of 17		NP_001350808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMF1	ENST00000398559.7	c.3041G>A	p.Arg1014Gln	missense_variant	Exon 16 of 17	1	NM_007114.3	ENSP00000381567.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000412 AC: 1 AN: 242566 Hom.: 0 AF XY: 0.00000759 AC XY: 1 AN XY: 131676

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000309

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: 0.00000481 AC: 7 AN: 1453926 Hom.: 0 Cov.: 31 AF XY: 0.00000415 AC XY: 3 AN XY: 722916

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000230

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000510

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3041G>A (p.R1014Q) alteration is located in exon 16 (coding exon 16) of the TMF1 gene. This alteration results from a G to A substitution at nucleotide position 3041, causing the arginine (R) at amino acid position 1014 to be replaced by a glutamine (Q). 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	0.37
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.55	D;.;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D;.;.
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;.;.
Sift4G	Uncertain	0.047	D;.;.
Polyphen		1.0	D;.;D
Vest4		0.95
MutPred		0.25		Loss of phosphorylation at S1015 (P = 0.0916);.;.;
MVP		0.93
MPC		0.54
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.74
gMVP		0.66

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

Other links and lift over

dbSNP: rs1485121884; hg19: chr3-69073303;