Variant chr4-70201464-A-C 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.539A>C(p.Tyr180Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000265 in 1,508,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

ODAM
NM_017855.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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:

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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=0.23746541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ODAM	NM_017855.4 linkuse as main transcript	c.539A>C	p.Tyr180Ser	missense_variant	8/12	ENST00000683306.1
ODAM	XM_047415863.1 linkuse as main transcript	c.590A>C	p.Tyr197Ser	missense_variant	8/11
ODAM	XM_047415864.1 linkuse as main transcript	c.548A>C	p.Tyr183Ser	missense_variant	7/11
ODAM	NM_001385579.1 linkuse as main transcript	c.529-794A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAM	ENST00000683306.1 linkuse as main transcript	c.539A>C	p.Tyr180Ser	missense_variant	8/12		NM_017855.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000839

AC:

AN:

238432

Hom.:

AF XY:

0.00000773

AC XY:

AN XY:

129300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000315

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.37e-7

AC:

AN:

1356930

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680604

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000825

AC:

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

Mar 23, 2022

The c.539A>C (p.Y180S) alteration is located in exon 7 (coding exon 7) of the ODAM gene. This alteration results from a A to C substitution at nucleotide position 539, causing the tyrosine (Y) at amino acid position 180 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.072

T;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.95

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.15

Sift

Benign

0.053

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.99

D;.

Vest4

0.72

MutPred

0.34

Loss of helix (P = 0.0444);.;

MVP

0.42

MPC

0.034

ClinPred

0.91

GERP RS

3.7

Varity_R

0.29

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 37

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