7-87171042-G-A

Position:

• chr7-87171042-G-A

Variant summary

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

The NM_001142327.2(DMTF1):​c.280G>A​(p.Glu94Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,230 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: 6.8e-7 (0 hom.)
• Consequence: DMTF1 NM_001142327.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.58

Genes affected

DMTF1 (HGNC:14603): (cyclin D binding myb like transcription factor 1) This gene encodes a transcription factor that contains a cyclin D-binding domain, three central Myb-like repeats, and two flanking acidic transactivation domains at the N- and C-termini. The encoded protein is induced by the oncogenic Ras signaling pathway and functions as a tumor suppressor by activating the transcription of ARF and thus the ARF-p53 pathway to arrest cell growth or induce apoptosis. It also activates the transcription of aminopeptidase N and may play a role in hematopoietic cell differentiation. The transcriptional activity of this protein is regulated by binding of D-cyclins. This gene is hemizygously deleted in approximately 40% of human non-small-cell lung cancer and is a potential prognostic and gene-therapy target for non-small-cell lung cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

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/exons	MANE	Protein	UniProt
DMTF1	NM_001142327.2	c.280G>A	p.Glu94Lys	missense_variant	5/18	ENST00000331242.12	NP_001135799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMTF1	ENST00000331242.12	c.280G>A	p.Glu94Lys	missense_variant	5/18	1	NM_001142327.2	ENSP00000332171.7
DMTF1	ENST00000394703.9	c.280G>A	p.Glu94Lys	missense_variant	7/20	1		ENSP00000378193.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460230 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726484

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2024

The c.280G>A (p.E94K) alteration is located in exon 7 (coding exon 3) of the DMTF1 gene. This alteration results from a G to A substitution at nucleotide position 280, causing the glutamic acid (E) at amino acid position 94 to be replaced by a lysine (K). 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	0.22
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.056	T;T;.;.;.;.;T;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	.;D;.;D;D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.;.;M;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.98	N;N;D;D;D;N;N;D;N
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.037	D;T;.;D;D;D;D;D;D
Polyphen		0.96	D;.;.;.;.;.;D;.;.
Vest4		0.50
MutPred		0.30		Gain of ubiquitination at E94 (P = 0.006);Gain of ubiquitination at E94 (P = 0.006);.;Gain of ubiquitination at E94 (P = 0.006);Gain of ubiquitination at E94 (P = 0.006);.;Gain of ubiquitination at E94 (P = 0.006);Gain of ubiquitination at E94 (P = 0.006);Gain of ubiquitination at E94 (P = 0.006);
MVP		0.34
MPC		0.39
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.51
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-86800358;