7-87164993-T-C

Position:

• chr7-87164993-T-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.52T>C​(p.Ser18Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DMTF1 NM_001142327.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49

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=0.25778016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMTF1	NM_001142327.2	c.52T>C	p.Ser18Pro	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.52T>C	p.Ser18Pro	missense_variant	3/18	1	NM_001142327.2	ENSP00000332171	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247728 Hom.: 0 AF XY: 0.00000746 AC XY: 1 AN XY: 133964

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458734 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725626

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

Sep 06, 2022

The c.52T>C (p.S18P) alteration is located in exon 5 (coding exon 1) of the DMTF1 gene. This alteration results from a T to C substitution at nucleotide position 52, causing the serine (S) at amino acid position 18 to be replaced by a proline (P). 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	0.19
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T;T;.;.;.;.;.;.;.;.;.;T;.;.;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	.;T;T;.;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.26	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.0	L;.;.;.;.;.;.;.;.;.;.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.4	N;N;D;D;D;D;D;D;D;D;D;N;D;.;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D;D;D;D;.;D;D;D;D;D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;.;.;.;.;.;.;.;D;.;.;.
Vest4		0.65
MutPred		0.14		Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);Gain of glycosylation at T15 (P = 0.0453);
MVP		0.30
MPC		0.39
ClinPred		0.50	D
GERP RS		5.6
Varity_R		0.56
gMVP		0.40

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: rs1375405223; hg19: chr7-86794309;