Variant 4-70202876-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017855.4(ODAM):c.769G>T(p.Ala257Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ODAM
NM_017855.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.135

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 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=0.050280303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAM	NM_017855.4 link	c.769G>T	p.Ala257Ser	missense_variant	10/12	ENST00000683306.1	NP_060325.3	A1E959
ODAM	NM_001385579.1 link	c.721G>T	p.Ala241Ser	missense_variant	9/11		NP_001372508.1
ODAM	XM_047415863.1 link	c.820G>T	p.Ala274Ser	missense_variant	10/11		XP_047271819.1
ODAM	XM_047415864.1 link	c.778G>T	p.Ala260Ser	missense_variant	9/11		XP_047271820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAM	ENST00000683306.1 link	c.769G>T	p.Ala257Ser	missense_variant	10/12		NM_017855.4	ENSP00000507531.1		A1E959

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250038

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460310

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726472

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Jan 02, 2024

The c.769G>T (p.A257S) alteration is located in exon 9 (coding exon 9) of the ODAM gene. This alteration results from a G to T substitution at nucleotide position 769, causing the alanine (A) at amino acid position 257 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

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.3

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0046

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.026

Sift

Benign

0.056

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.041

B;.;.

Vest4

0.17

MutPred

0.16

Gain of relative solvent accessibility (P = 0.0023);.;.;

MVP

0.16

MPC

0.0078

ClinPred

0.036

GERP RS

-0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.047

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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