4-70198084-A-T

Variant names:

• chr4-70198084-A-T
• rs201514554
• NM_017855.4:c.302A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017855.4(ODAM):​c.302A>T​(p.Gln101Leu) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q101R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODAM NM_017855.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20625457).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017855.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAM	NM_017855.4	MANE Select	c.302A>T	p.Gln101Leu	missense	Exon 5 of 12	NP_060325.3
	ODAM	NM_001385579.1		c.302A>T	p.Gln101Leu	missense	Exon 5 of 11	NP_001372508.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAM	ENST00000683306.1	MANE Select	c.302A>T	p.Gln101Leu	missense	Exon 5 of 12	ENSP00000507531.1	A1E959
	ODAM	ENST00000396094.6	TSL:5	c.302A>T	p.Gln101Leu	missense	Exon 4 of 11	ENSP00000379401.2	A1E959
	ODAM	ENST00000955828.1		c.302A>T	p.Gln101Leu	missense	Exon 5 of 12	ENSP00000625887.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.1
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.051
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.029	D
Polyphen		0.90	P
Vest4		0.46
MutPred		0.35		Gain of helix (P = 0.0325)
MVP		0.51
MPC		0.020
ClinPred		0.70	D
GERP RS		2.1
PromoterAI		0.0080	Neutral
Varity_R		0.43
gMVP		0.42
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs201514554; hg19: chr4-71063801;