chr7-87164996-G-C

Position:

• chr7-87164996-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142327.2(DMTF1):​c.55G>C​(p.Val19Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,184 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.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DMTF1 NM_001142327.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

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]

DMTF1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18183258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMTF1	NM_001142327.2	c.55G>C	p.Val19Leu	missense_variant	3/18	ENST00000331242.12	NP_001135799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMTF1	ENST00000331242.12	c.55G>C	p.Val19Leu	missense_variant	3/18	1	NM_001142327.2	ENSP00000332171.7
DMTF1	ENST00000394703.9	c.55G>C	p.Val19Leu	missense_variant	5/20	1		ENSP00000378193.5
DMTF1	ENST00000579592.5	c.*7G>C		downstream_gene_variant		4		ENSP00000463735.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

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

Sep 02, 2024

The c.55G>C (p.V19L) alteration is located in exon 5 (coding exon 1) of the DMTF1 gene. This alteration results from a G to C substitution at nucleotide position 55, causing the valine (V) at amino acid position 19 to be replaced by a leucine (L). 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	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;T;.;.;.;.;.;.;.;.;.;T;.;.;.
Eigen	Benign	0.034
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.;.;.;.;.;.;.;.;.;.;L;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.85	N;N;D;D;D;D;D;N;N;D;D;N;N;.;N
REVEL	Benign	0.047
Sift	Benign	0.13	T;D;T;T;T;.;T;T;T;T;T;T;T;.;T
Sift4G	Benign	0.18	T;T;T;D;T;D;D;T;T;T;D;T;T;D;T
Polyphen		0.0090	B;.;.;.;.;.;.;.;.;.;.;B;.;.;.
Vest4		0.37
MutPred		0.17		Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);Loss of catalytic residue at V19 (P = 0.0068);
MVP		0.22
MPC		0.30
ClinPred		0.57	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
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

LitVar

Other links and lift over

dbSNP: rs915588847; hg19: chr7-86794312;