Variant 4-75564323-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_178497.5(ODAPH):c.277T>C(p.Ser93Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 1,614,162 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 73 hom. )

Consequence

ODAPH
NM_178497.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.24

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036925077).

BP6

Variant 4-75564323-T-C is Benign according to our data. Variant chr4-75564323-T-C is described in ClinVar as [Benign]. Clinvar id is 788782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAPH	NM_178497.5 linkuse as main transcript	c.277T>C	p.Ser93Pro	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.277T>C	p.Ser93Pro	missense_variant	2/2	1	NM_178497.5	ENSP00000311307.5	Q17RF5-1
ODAPH	ENST00000511093.5 linkuse as main transcript	n.*220-65T>C		intron_variant		1		ENSP00000421429.1	D6RFW7
ODAPH	ENST00000435974.2 linkuse as main transcript	c.321T>C	p.Leu107Leu	synonymous_variant	3/3	2		ENSP00000406925.2	Q17RF5-2
ODAPH	ENST00000616557.1 linkuse as main transcript	c.207-65T>C		intron_variant		3		ENSP00000479147.1	A0A087WV33

Frequencies

GnomAD3 genomes

AF:

0.00672

AC:

1023

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00878

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00754

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00634

AC:

1594

AN:

251492

Hom.:

AF XY:

0.00633

AC XY:

860

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00323

Gnomad FIN exome

AF:

0.00674

Gnomad NFE exome

AF:

0.00955

Gnomad OTH exome

AF:

0.00847

GnomAD4 exome

AF:

0.00918

AC:

13421

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00897

AC XY:

6520

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.00601

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00344

Gnomad4 FIN exome

AF:

0.00608

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00791

GnomAD4 genome

AF:

0.00672

AC:

1023

AN:

152280

Hom.:

Cov.:

AF XY:

0.00655

AC XY:

488

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00754

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00983

Hom.:

Bravo

AF:

0.00691

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0127

AC:

109

ExAC

AF:

0.00622

AC:

755

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0106

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.00039

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00037

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

PROVEAN

Benign

2.5

REVEL

Benign

0.023

Sift

Benign

0.98

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.062

MVP

0.014

ClinPred

0.00031

GERP RS

2.5

Varity_R

0.059

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