rs1880639329

Variant names:

• chr12-68809225-A-C
• NM_002392.6:c.32A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-68809225-A-C
• chr12-68809225-A-G
• chr12-68809225-A-T

Variant summary

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

The NM_002392.6(MDM2):​c.32A>C​(p.Asn11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MDM2 NM_002392.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756

Genes affected

MDM2 (HGNC:6973): (MDM2 proto-oncogene) This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells. [provided by RefSeq, Jun 2013]

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=0.14952746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDM2	NM_002392.6	c.32A>C	p.Asn11Thr	missense_variant	Exon 2 of 11	ENST00000258149.11	NP_002383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDM2	ENST00000258149.11	c.32A>C	p.Asn11Thr	missense_variant	Exon 2 of 11	1	NM_002392.6	ENSP00000258149.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461464 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727036

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	.;T;T;T;D;T;.;.;.;.;T;.;.;.;.;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.87	D;D;D;D;D;D;D;D;.;.;.;D;D;D;.;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;.;.;.;L;.;.;.;.;.;.;L;L;.;.;L;.
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	.;D;N;N;N;N;D;D;N;N;N;N;D;N;D;N;N
REVEL	Benign	0.028
Sift	Uncertain	0.015	.;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D
Sift4G	Benign	0.43	T;D;D;T;T;D;D;D;D;D;D;D;D;T;D;D;T
Polyphen		0.079	B;.;.;B;B;.;.;.;.;.;.;B;.;.;.;.;.
Vest4		0.21
MutPred		0.28		.;Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);.;Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);Gain of catalytic residue at C2 (P = 0.0032);
MVP		0.51
ClinPred		0.30	T
GERP RS		3.5
Varity_R		0.10
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-69203005;