4-70197996-C-A

Position:

• chr4-70197996-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017855.4(ODAM):​c.214C>A​(p.Leu72Ile) 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. 15/21 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.374

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06702259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAM	NM_017855.4	c.214C>A	p.Leu72Ile	missense_variant	5/12	ENST00000683306.1	NP_060325.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAM	ENST00000683306.1	c.214C>A	p.Leu72Ile	missense_variant	5/12		NM_017855.4	ENSP00000507531.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 12, 2024

The c.214C>A (p.L72I) alteration is located in exon 4 (coding exon 4) of the ODAM gene. This alteration results from a C to A substitution at nucleotide position 214, causing the leucine (L) at amino acid position 72 to be replaced by an isoleucine (I). 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	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.032	D;D;D
Sift4G	Benign	0.24	T;T;T
Polyphen		0.56	P;.;.
Vest4		0.32
MutPred		0.17		Loss of catalytic residue at L72 (P = 0.0233);.;.;
MVP		0.14
MPC		0.028
ClinPred		0.33	T
GERP RS		3.0
Varity_R		0.067
gMVP		0.12

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: rs1729411588; hg19: chr4-71063713;