7-87179586-G-A

Position:

• chr7-87179586-G-A

Variant summary

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

The NM_001142327.2(DMTF1):​c.561G>A​(p.Met187Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DMTF1 NM_001142327.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.92

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.561G>A	p.Met187Ile	missense_variant	8/18	ENST00000331242.12	NP_001135799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMTF1	ENST00000331242.12	c.561G>A	p.Met187Ile	missense_variant	8/18	1	NM_001142327.2	ENSP00000332171	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jul 20, 2021

The c.561G>A (p.M187I) alteration is located in exon 10 (coding exon 6) of the DMTF1 gene. This alteration results from a G to A substitution at nucleotide position 561, causing the methionine (M) at amino acid position 187 to be replaced by an isoleucine (I). 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	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;.;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;.;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.1	N;N;N;N;D
REVEL	Uncertain	0.34
Sift	Benign	0.069	T;T;T;T;D
Sift4G	Uncertain	0.025	D;T;D;D;D
Polyphen		0.97	D;.;.;D;.
Vest4		0.73
MutPred		0.37		Loss of ubiquitination at K189 (P = 0.0547);Loss of ubiquitination at K189 (P = 0.0547);.;Loss of ubiquitination at K189 (P = 0.0547);Loss of ubiquitination at K189 (P = 0.0547);
MVP		0.70
MPC		2.5
ClinPred		0.90	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr7-86808902;