Genetic Variant NM_017855.4:c.658G>A (chr4-70202765-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017855.4(ODAM):c.658G>A(p.Glu220Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,609,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ODAM
NM_017855.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.859

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04819283).

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.658G>A	p.Glu220Lys	missense	Exon 10 of 12	NP_060325.3
	ODAM	NM_001385579.1		c.610G>A	p.Glu204Lys	missense	Exon 9 of 11	NP_001372508.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ODAM	ENST00000683306.1	MANE Select	c.658G>A	p.Glu220Lys	missense	Exon 10 of 12	ENSP00000507531.1	A1E959
ODAM	ENST00000396094.6	TSL:5	c.658G>A	p.Glu220Lys	missense	Exon 9 of 11	ENSP00000379401.2	A1E959
ODAM	ENST00000955828.1		c.658G>A	p.Glu220Lys	missense	Exon 10 of 12	ENSP00000625887.1

Frequencies

GnomAD3 genomes

AF:

0.0000791

AC:

AN:

151742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.0000324

AC:

AN:

247074

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000551

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1457744

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

725160

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33282

American (AMR)

AF:

0.0000226

AC:

AN:

44238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.000101

AC:

AN:

39556

South Asian (SAS)

AF:

0.000152

AC:

AN:

85804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109874

Other (OTH)

AF:

0.000332

AC:

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000791

AC:

AN:

151742

Hom.:

Cov.:

AF XY:

0.0000945

AC XY:

AN XY:

74064

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000582

AC:

AN:

5154

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67876

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.63

M_CAP

Benign

0.0098

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PhyloP100

0.86

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.6

REVEL

Benign

0.034

Sift

Benign

0.21

Sift4G

Benign

0.79

Polyphen

0.10

Vest4

0.28

MutPred

0.29

Gain of glycosylation at Y224 (P = 0.0155)

MVP

0.16

MPC

0.0077

ClinPred

0.018

GERP RS

2.3

Varity_R

0.10

gMVP

0.079

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over