NM_002539.3:c.1373G>C

Variant names:

• chr2-10440737-C-G
• NM_002539.3:c.1373G>C

Variant summary

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

The NM_002539.3(ODC1):​c.1373G>C​(p.Ser458Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODC1 NM_002539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19

Genes affected

ODC1 (HGNC:8109): (ornithine decarboxylase 1) This gene encodes the rate-limiting enzyme of the polyamine biosynthesis pathway which catalyzes ornithine to putrescine. The activity level for the enzyme varies in response to growth-promoting stimuli and exhibits a high turnover rate in comparison to other mammalian proteins. Originally localized to both chromosomes 2 and 7, the gene encoding this enzyme has been determined to be located on 2p25, with a pseudogene located on 7q31-qter. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Dec 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=0.1380617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3	c.1373G>C	p.Ser458Thr	missense_variant	Exon 12 of 12	ENST00000234111.9	NP_002530.1
ODC1	NM_001287189.2	c.1373G>C	p.Ser458Thr	missense_variant	Exon 12 of 12		NP_001274118.1
ODC1	NM_001287190.2	c.1373G>C	p.Ser458Thr	missense_variant	Exon 12 of 12		NP_001274119.1
ODC1	NM_001287188.2	c.986G>C	p.Ser329Thr	missense_variant	Exon 12 of 12		NP_001274117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.1373G>C	p.Ser458Thr	missense_variant	Exon 12 of 12	1	NM_002539.3	ENSP00000234111.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 13, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	-0.075
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.59	.;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.083
Sift	Benign	0.15	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.23		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.33
MPC		0.36
ClinPred		0.48	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.42

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: chr2-10580863;