7-87166587-T-G

Position:

• chr7-87166587-T-G

Variant summary

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

The NM_001142327.2(DMTF1):​c.214T>G​(p.Ser72Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMTF1 NM_001142327.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2569375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMTF1	NM_001142327.2	c.214T>G	p.Ser72Ala	missense_variant	4/18	ENST00000331242.12	NP_001135799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMTF1	ENST00000331242.12	c.214T>G	p.Ser72Ala	missense_variant	4/18	1	NM_001142327.2	ENSP00000332171	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000301 Hom.: 0

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

Apr 03, 2023

The c.214T>G (p.S72A) alteration is located in exon 6 (coding exon 2) of the DMTF1 gene. This alteration results from a T to G substitution at nucleotide position 214, causing the serine (S) at amino acid position 72 to be replaced by an alanine (A). 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	0.14
BayesDel_addAF	Benign	-0.0097	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.;.;.;.;.;T;.;.
Eigen	Benign	-0.041
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	.;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.;.;.;.;.;N;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	N;N;.;D;N;N;D;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D;D;.;D;D;D;D;D;D;T
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0020	B;.;.;.;.;.;.;B;.;.
Vest4		0.56
MutPred		0.31		Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);
MVP		0.24
MPC		0.51
ClinPred		0.77	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.26

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: rs1201197951; hg19: chr7-86795903;