NM_178497.5:c.89C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178497.5(ODAPH):c.89C>T(p.Pro30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,613,544 control chromosomes in the GnomAD database, including 44,961 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4691 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40270 hom. )

Consequence

ODAPH
NM_178497.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.96

Publications

20 publications found

Variant links:

Genes affected

ODAPH (HGNC:26300): (odontogenesis associated phosphoprotein) Dental enamel forms the outer cap of teeth and is the hardest substance found in vertebrates. This gene is thought to encode an extracellular matrix acidic phosphoprotein that has a function in enamel mineralization during amelogenesis. Mutations in this gene are associated with recessive hypomineralized amelogenesis imperfecta. [provided by RefSeq, Oct 2012]

ODAPH Gene-Disease associations (from GenCC):

amelogenesis imperfecta hypomaturation type 2A4
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)
amelogenesis imperfecta type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ODAPH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005912304).

BP6

Variant 4-75564135-C-T is Benign according to our data. Variant chr4-75564135-C-T is described in CliVar as Benign. Clinvar id is 262959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-75564135-C-T is described in CliVar as Benign. Clinvar id is 262959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-75564135-C-T is described in CliVar as Benign. Clinvar id is 262959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-75564135-C-T is described in CliVar as Benign. Clinvar id is 262959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-75564135-C-T is described in CliVar as Benign. Clinvar id is 262959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-75564135-C-T is described in CliVar as Benign. Clinvar id is 262959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAPH	NM_178497.5 link	c.89C>T	p.Pro30Leu	missense_variant	Exon 2 of 2	ENST00000311623.9	NP_848592.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAPH	ENST00000311623.9 link	c.89C>T	p.Pro30Leu	missense_variant	Exon 2 of 2	1	NM_178497.5	ENSP00000311307.5		Q17RF5-1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36785

AN:

151942

Hom.:

4682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.211

GnomAD2 exomes

AF:

0.215

AC:

54175

AN:

251406

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.232

AC:

338657

AN:

1461484

Hom.:

40270

Cov.:

AF XY:

0.231

AC XY:

167753

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.304

AC:

10181

AN:

33474

American (AMR)

AF:

0.123

AC:

5503

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3919

AN:

26134

East Asian (EAS)

AF:

0.277

AC:

11000

AN:

39700

South Asian (SAS)

AF:

0.204

AC:

17590

AN:

86248

European-Finnish (FIN)

AF:

0.251

AC:

13412

AN:

53412

Middle Eastern (MID)

AF:

0.148

AC:

852

AN:

5768

European-Non Finnish (NFE)

AF:

0.236

AC:

262892

AN:

1111644

Other (OTH)

AF:

0.220

AC:

13308

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

14396

28791

43187

57582

71978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9010

18020

27030

36040

45050

<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:

0.242

AC:

36824

AN:

152060

Hom.:

4691

Cov.:

AF XY:

0.240

AC XY:

17859

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.300

AC:

12419

AN:

41460

American (AMR)

AF:

0.175

AC:

2672

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

487

AN:

3472

East Asian (EAS)

AF:

0.248

AC:

1285

AN:

5172

South Asian (SAS)

AF:

0.206

AC:

995

AN:

4820

European-Finnish (FIN)

AF:

0.254

AC:

2683

AN:

10554

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.230

AC:

15621

AN:

67982

Other (OTH)

AF:

0.212

AC:

448

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1410

2820

4230

5640

7050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.230

Hom.:

16006

Bravo

AF:

0.237

TwinsUK

AF:

0.234

AC:

868

ALSPAC

AF:

0.231

AC:

889

ESP6500AA

AF:

0.307

AC:

1354

ESP6500EA

AF:

0.234

AC:

2014

ExAC

AF:

0.223

AC:

27018

Asia WGS

AF:

0.233

AC:

812

AN:

3478

EpiCase

AF:

0.217

EpiControl

AF:

0.221

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.97

PhyloP100

2.0

PROVEAN

Benign

-1.4

REVEL

Benign

0.13

Sift

Benign

0.25

Sift4G

Benign

0.37

Vest4

0.079

MPC

0.24

ClinPred

0.028

GERP RS

2.8

Varity_R

0.19

gMVP

0.016

Mutation Taster

=93/7

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over