NM_001142327.2:c.273A>G

Variant names:

• chr7-87171035-A-G
• rs3747807
• NM_001142327.2:c.273A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001142327.2(DMTF1):​c.273A>G​(p.Ala91Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,610,518 control chromosomes in the GnomAD database, including 587,281 homozygotes. 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 0.84 (54285 hom., cov: 32)
  • Exomes 𝑓: 0.85 (532996 hom.)
• Consequence: DMTF1 NM_001142327.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMTF1	NM_001142327.2	c.273A>G	p.Ala91Ala	synonymous_variant	Exon 5 of 18	ENST00000331242.12	NP_001135799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMTF1	ENST00000331242.12	c.273A>G	p.Ala91Ala	synonymous_variant	Exon 5 of 18	1	NM_001142327.2	ENSP00000332171.7
DMTF1	ENST00000394703.9	c.273A>G	p.Ala91Ala	synonymous_variant	Exon 7 of 20	1		ENSP00000378193.5

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128156 AN: 152060 Hom.: 54241 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.855

GnomAD2 exomes AF: 0.817 AC: 204748 AN: 250554 AF XY: 0.826

Gnomad AFR exome AF: 0.819

Gnomad AMR exome AF: 0.660

Gnomad ASJ exome AF: 0.896

Gnomad EAS exome AF: 0.637

Gnomad FIN exome AF: 0.872

Gnomad NFE exome AF: 0.872

Gnomad OTH exome AF: 0.840

GnomAD4 exome AF: 0.852 AC: 1242810 AN: 1458340 Hom.: 532996 Cov.: 37 AF XY: 0.853 AC XY: 619013 AN XY: 725628

African (AFR) AF: 0.825 AC: 27503 AN: 33344

American (AMR) AF: 0.678 AC: 30169 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 23325 AN: 26100

East Asian (EAS) AF: 0.573 AC: 22721 AN: 39638

South Asian (SAS) AF: 0.828 AC: 71237 AN: 86044

European-Finnish (FIN) AF: 0.873 AC: 46589 AN: 53368

Middle Eastern (MID) AF: 0.919 AC: 5295 AN: 5760

European-Non Finnish (NFE) AF: 0.870 AC: 964659 AN: 1109292

Other (OTH) AF: 0.851 AC: 51312 AN: 60276

GnomAD4 genome AF: 0.843 AC: 128253 AN: 152178 Hom.: 54285 Cov.: 32 AF XY: 0.843 AC XY: 62696 AN XY: 74416

African (AFR) AF: 0.825 AC: 34237 AN: 41516

American (AMR) AF: 0.798 AC: 12184 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3103 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3277 AN: 5166

South Asian (SAS) AF: 0.815 AC: 3927 AN: 4816

European-Finnish (FIN) AF: 0.878 AC: 9312 AN: 10606

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59313 AN: 68006

Other (OTH) AF: 0.852 AC: 1803 AN: 2116

Alfa AF: 0.857 Hom.: 121112

Bravo AF: 0.832

Asia WGS AF: 0.686 AC: 2389 AN: 3478

EpiCase AF: 0.876

EpiControl AF: 0.881

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3747807; hg19: chr7-86800351; COSMIC: COSV58685489; COSMIC: COSV58685489;