rs1137806

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

amelogenesis imperfecta, type 3A
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

FAM83H 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=0.0052135885).

BP6

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

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5 link	c.1493C>T	p.Pro498Leu	missense_variant	Exon 5 of 5	ENST00000388913.4	NP_940890.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FAM83H	ENST00000388913.4 link	c.1493C>T	p.Pro498Leu	missense_variant	Exon 5 of 5	5	NM_198488.5	ENSP00000373565.3
FAM83H	ENST00000650760.1 link	c.2096C>T	p.Pro699Leu	missense_variant	Exon 5 of 5			ENSP00000499217.1
FAM83H	ENST00000395103.2 link	n.671C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000378535.2

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

GnomAD2 exomes

AF:

0.165

AC:

28947

AN:

175774

AF XY:

0.170

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 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

African (AFR)

AF:

0.0207

AC:

683

AN:

32978

American (AMR)

AF:

0.176

AC:

6716

AN:

38086

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

3775

AN:

25426

East Asian (EAS)

AF:

0.253

AC:

9732

AN:

38468

South Asian (SAS)

AF:

0.272

AC:

22468

AN:

82564

European-Finnish (FIN)

AF:

0.168

AC:

6411

AN:

38212

Middle Eastern (MID)

AF:

0.123

AC:

507

AN:

4124

European-Non Finnish (NFE)

AF:

0.125

AC:

137152

AN:

1097632

Other (OTH)

AF:

0.147

AC:

8666

AN:

59006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

10101

20202

30302

40403

50504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5198

10396

15594

20792

25990

<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:

0.113

AC:

17118

AN:

151944

Hom.:

1362

Cov.:

AF XY:

0.119

AC XY:

8835

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.0253

AC:

1051

AN:

41526

American (AMR)

AF:

0.145

AC:

2220

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

500

AN:

3472

East Asian (EAS)

AF:

0.249

AC:

1284

AN:

5160

South Asian (SAS)

AF:

0.293

AC:

1417

AN:

4834

European-Finnish (FIN)

AF:

0.166

AC:

1733

AN:

10462

Middle Eastern (MID)

AF:

0.103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.124

AC:

8394

AN:

67914

Other (OTH)

AF:

0.136

AC:

287

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

767

1533

2300

3066

3833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.0891

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

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amelogenesis imperfecta, hypocalcification type

Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

0.13

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Pathogenic

(source)

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

PhyloP100

5.9

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

Mutation Taster

=94/6

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