rs142153660

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.1910C>T(p.Pro637Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,586,832 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 110 hom., cov: 34)

Exomes 𝑓: 0.023 ( 540 hom. )

Consequence

FAM83H
NM_198488.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.432

Publications

6 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=0.0016061664).

BP6

Variant 8-143727551-G-A is Benign according to our data. Variant chr8-143727551-G-A is described in ClinVar as Benign. ClinVar VariationId is 263134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5 link	c.1910C>T	p.Pro637Leu	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.1910C>T	p.Pro637Leu	missense_variant	Exon 5 of 5	5	NM_198488.5	ENSP00000373565.3
FAM83H	ENST00000650760.1 link	c.2513C>T	p.Pro838Leu	missense_variant	Exon 5 of 5			ENSP00000499217.1
FAM83H	ENST00000395103.2 link	n.1088C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000378535.2

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5041

AN:

152120

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0667

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0524

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0453

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.0541

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0306

GnomAD2 exomes

AF:

0.0246

AC:

5099

AN:

206988

AF XY:

0.0260

show subpopulations

Gnomad AFR exome

AF:

0.0672

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.0000600

Gnomad FIN exome

AF:

0.00560

Gnomad NFE exome

AF:

0.0192

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0226

AC:

32408

AN:

1434604

Hom.:

540

Cov.:

AF XY:

0.0235

AC XY:

16763

AN XY:

713182

show subpopulations

African (AFR)

AF:

0.0682

AC:

2227

AN:

32660

American (AMR)

AF:

0.0155

AC:

677

AN:

43606

Ashkenazi Jewish (ASJ)

AF:

0.0534

AC:

1374

AN:

25726

East Asian (EAS)

AF:

0.000102

AC:

AN:

39096

South Asian (SAS)

AF:

0.0487

AC:

4153

AN:

85202

European-Finnish (FIN)

AF:

0.00715

AC:

271

AN:

37920

Middle Eastern (MID)

AF:

0.0559

AC:

284

AN:

5076

European-Non Finnish (NFE)

AF:

0.0198

AC:

21902

AN:

1105796

Other (OTH)

AF:

0.0255

AC:

1516

AN:

59522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

2017

4033

6050

8066

10083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.0332

AC:

5054

AN:

152228

Hom.:

110

Cov.:

AF XY:

0.0324

AC XY:

2410

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0668

AC:

2777

AN:

41556

American (AMR)

AF:

0.0232

AC:

355

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0524

AC:

182

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5146

South Asian (SAS)

AF:

0.0455

AC:

220

AN:

4832

European-Finnish (FIN)

AF:

0.00621

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0548

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0189

AC:

1288

AN:

67988

Other (OTH)

AF:

0.0303

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

244

488

733

977

1221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0295

Hom.:

Bravo

AF:

0.0354

TwinsUK

AF:

0.0237

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.0524

AC:

158

ESP6500EA

AF:

0.0215

AC:

151

ExAC

AF:

0.0226

AC:

2574

Asia WGS

AF:

0.0190

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.10

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

PhyloP100

0.43

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.9

REVEL

Benign

0.037

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Polyphen

0.42

Vest4

0.022

MPC

0.33

ClinPred

0.0092

GERP RS

3.0

Varity_R

0.088

gMVP

0.22

Mutation Taster

=89/11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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