4-70202844-C-A

Position:

• chr4-70202844-C-A

Variant summary

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

The NM_017855.4(ODAM):​c.737C>A​(p.Pro246Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODAM NM_017855.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.151

Genes affected

ODAM (HGNC:26043): (odontogenic, ameloblast associated) Involved in several processes, including positive regulation of GTPase activity; positive regulation of epithelial cell proliferation involved in wound healing; and positive regulation of macromolecule metabolic process. Located in several cellular components, including extracellular space; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07004401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAM	NM_017855.4	c.737C>A	p.Pro246Gln	missense_variant	10/12	ENST00000683306.1	NP_060325.3
ODAM	NM_001385579.1	c.689C>A	p.Pro230Gln	missense_variant	9/11		NP_001372508.1
ODAM	XM_047415863.1	c.788C>A	p.Pro263Gln	missense_variant	10/11		XP_047271819.1
ODAM	XM_047415864.1	c.746C>A	p.Pro249Gln	missense_variant	9/11		XP_047271820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAM	ENST00000683306.1	c.737C>A	p.Pro246Gln	missense_variant	10/12		NM_017855.4	ENSP00000507531.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.0050	T;.;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.059
Sift	Benign	0.64	T;T;T
Sift4G	Benign	0.62	T;T;T
Polyphen		0.035	B;.;.
Vest4		0.081
MutPred		0.24		Loss of glycosylation at P246 (P = 0.0173);.;.;
MVP		0.17
MPC		0.041
ClinPred		0.71	D
GERP RS		1.9
Varity_R		0.099
gMVP		0.041

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: chr4-71068561;