Variant rs1137806 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_198488.5(FAM83H):c.1493C>T(p.Pro498Leu) variant causes a missense change. The variant allele was found at a frequency of 0.136 in 1,568,440 control chromosomes in the GnomAD database, including 16,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1362 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15262 hom. )

Consequence

FAM83H
NM_198488.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.89

Variant links:

Genes affected

FAM83H (HGNC:24797): (family with sequence similarity 83 member H) The protein encoded by this gene plays an important role in the structural development and calcification of tooth enamel. Defects in this gene are a cause of amelogenesis imperfecta type 3 (AI3). [provided by RefSeq, Mar 2010]

FAM83H 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=0.0052135885).

BP6

Variant 8-143727968-G-A is Benign according to our data. Variant chr8-143727968-G-A is described in ClinVar as [Benign]. Clinvar id is 263132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-143727968-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83H	NM_198488.5 linkuse as main transcript	c.1493C>T	p.Pro498Leu	missense_variant	5/5	ENST00000388913.4	NP_940890.4	Q6ZRV2Q71RB4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM83H	ENST00000388913.4 linkuse as main transcript	c.1493C>T	p.Pro498Leu	missense_variant	5/5	5	NM_198488.5	ENSP00000373565.3	Q6ZRV2
FAM83H	ENST00000650760.1 linkuse as main transcript	c.2096C>T	p.Pro699Leu	missense_variant	5/5			ENSP00000499217.1	A0A494C1T9
FAM83H	ENST00000395103.2 linkuse as main transcript	n.671C>T		non_coding_transcript_exon_variant	1/2	2		ENSP00000378535.2	J3KPS2

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17125

AN:

151832

Hom.:

1360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.102

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.165

AC:

28947

AN:

175774

Hom.:

2789

AF XY:

0.170

AC XY:

16539

AN XY:

97492

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.249

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.138

AC:

196110

AN:

1416496

Hom.:

15262

Cov.:

AF XY:

0.142

AC XY:

99957

AN XY:

702418

show subpopulations

Gnomad4 AFR exome

AF:

0.0207

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.253

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.113

AC:

17118

AN:

151944

Hom.:

1362

Cov.:

AF XY:

0.119

AC XY:

8835

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.145

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.249

Gnomad4 SAS

AF:

0.293

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.0891

Hom.:

157

Bravo

AF:

0.106

TwinsUK

AF:

0.125

AC:

463

ALSPAC

AF:

0.122

AC:

470

ESP6500AA

AF:

0.0203

AC:

ESP6500EA

AF:

0.108

AC:

767

ExAC

AF:

0.137

AC:

15023

Asia WGS

AF:

0.272

AC:

942

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 11, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Amelogenesis imperfecta, hypocalcification type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.66

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.16

Sift

Uncertain

0.029

Sift4G

Uncertain

0.057

Polyphen

1.0

Vest4

0.10

MPC

0.77

ClinPred

0.021

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.11

gMVP

0.45

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