Variant chr4-75564372-G-A 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.326G>A(p.Arg109His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,613,812 control chromosomes in the GnomAD database, including 10,629 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 0.11 ( 1078 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9551 hom. )

Consequence

ODAPH
NM_178497.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.285

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:

ODAPH (HGNC:):

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=0.0018441081).

BP6

Variant 4-75564372-G-A is Benign according to our data. Variant chr4-75564372-G-A is described in ClinVar as [Benign]. Clinvar id is 1262065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAPH	NM_178497.5 linkuse as main transcript	c.326G>A	p.Arg109His	missense_variant	2/2	ENST00000311623.9	NP_848592.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ODAPH	ENST00000311623.9 linkuse as main transcript	c.326G>A	p.Arg109His	missense_variant	2/2	1	NM_178497.5	ENSP00000311307.5	Q17RF5-1
ODAPH	ENST00000511093.5 linkuse as main transcript	n.*220-16G>A		intron_variant		1		ENSP00000421429.1	D6RFW7
ODAPH	ENST00000435974.2 linkuse as main transcript	c.370G>A	p.Val124Ile	missense_variant	3/3	2		ENSP00000406925.2	Q17RF5-2
ODAPH	ENST00000616557.1 linkuse as main transcript	c.207-16G>A		intron_variant		3		ENSP00000479147.1	A0A087WV33

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

16987

AN:

151896

Hom.:

1073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0831

Gnomad ASJ

AF:

0.0968

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0566

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0972

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.115

AC:

29012

AN:

251456

Hom.:

1999

AF XY:

0.119

AC XY:

16206

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.0820

Gnomad ASJ exome

AF:

0.0964

Gnomad EAS exome

AF:

0.182

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.0725

Gnomad NFE exome

AF:

0.0971

Gnomad OTH exome

AF:

0.0960

GnomAD4 exome

AF:

0.108

AC:

158467

AN:

1461798

Hom.:

9551

Cov.:

AF XY:

0.111

AC XY:

80535

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.0829

Gnomad4 ASJ exome

AF:

0.0955

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.0721

Gnomad4 NFE exome

AF:

0.0999

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.112

AC:

17015

AN:

152014

Hom.:

1078

Cov.:

AF XY:

0.113

AC XY:

8382

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0835

Gnomad4 ASJ

AF:

0.0968

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.0566

Gnomad4 NFE

AF:

0.0973

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0990

Hom.:

1948

Bravo

AF:

0.114

TwinsUK

AF:

0.0982

AC:

364

ALSPAC

AF:

0.0952

AC:

367

ESP6500AA

AF:

0.135

AC:

596

ESP6500EA

AF:

0.101

AC:

867

ExAC

AF:

0.120

AC:

14515

Asia WGS

AF:

0.177

AC:

615

AN:

3478

EpiCase

AF:

0.0925

EpiControl

AF:

0.0950

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.83

REVEL

Benign

0.093

Sift

Benign

0.20

Sift4G

Benign

0.18

Polyphen

0.93

Vest4

0.11

ClinPred

0.010

GERP RS

-4.6

Varity_R

0.014

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