Variant rs2306175 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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:2

Conservation

PhyloP100: 1.96

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	UniProt
ODAPH	NM_178497.5 linkuse as main transcript	c.89C>T	p.Pro30Leu	missense_variant	2/2	ENST00000311623.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAPH	ENST00000311623.9 linkuse as main transcript	c.89C>T	p.Pro30Leu	missense_variant	2/2	1	NM_178497.5	P1	Q17RF5-1
ODAPH	ENST00000511093.5 linkuse as main transcript	c.*102C>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	1
ODAPH	ENST00000435974.2 linkuse as main transcript	c.133C>T	p.Leu45Phe	missense_variant	3/3	2			Q17RF5-2
ODAPH	ENST00000616557.1 linkuse as main transcript	c.89C>T	p.Pro30Leu	missense_variant	2/3	3

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

GnomAD3 exomes

AF:

0.215

AC:

54175

AN:

251406

Hom.:

6282

AF XY:

0.217

AC XY:

29465

AN XY:

135888

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 SAS exome

AF:

0.205

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

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.251

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.242

AC:

36824

AN:

152060

Hom.:

4691

Cov.:

AF XY:

0.240

AC XY:

17859

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.227

Hom.:

10428

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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

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

MutationTaster

Benign

1.0

P;P

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

gMVP

0.016

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

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