Variant 4-70197293-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017855.4(ODAM):c.113A>G(p.Asn38Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,444,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

ODAM
NM_017855.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

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]

ODAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.26195455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAM	NM_017855.4 link	c.113A>G	p.Asn38Ser	missense_variant	4/12	ENST00000683306.1	NP_060325.3	A1E959

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ODAM	ENST00000683306.1 link	c.113A>G	p.Asn38Ser	missense_variant	4/12		NM_017855.4	ENSP00000507531.1	A1E959
ODAM	ENST00000396094.6 link	c.113A>G	p.Asn38Ser	missense_variant	3/11	5		ENSP00000379401.2	A1E959
ODAM	ENST00000510709.6 link	c.71A>G	p.Asn24Ser	missense_variant	2/8	5		ENSP00000423070.2	D6RA81

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.74e-7

AC:

AN:

1292606

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

651888

show subpopulations

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:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.113A>G (p.N38S) alteration is located in exon 3 (coding exon 3) of the ODAM gene. This alteration results from a A to G substitution at nucleotide position 113, causing the asparagine (N) at amino acid position 38 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.13

T;T

Polyphen

1.0

D;.

Vest4

0.65

MutPred

0.14

Loss of glycosylation at P43 (P = 0.0662);.;

MVP

0.35

MPC

0.030

ClinPred

0.97

GERP RS

4.7

Varity_R

0.40

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over