rs117987215

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_StrongBS1BS2

The NM_198488.5(FAM83H):c.3059G>A(p.Arg1020Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00901 in 1,605,694 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1020W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0065 ( 8 hom., cov: 34)

Exomes 𝑓: 0.0093 ( 83 hom. )

Consequence

FAM83H
NM_198488.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.708

Publications

7 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: Labcorp Genetics (formerly Invitae), Orphanet

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=0.004142016).

BP6

Variant 8-143726402-C-T is Benign according to our data. Variant chr8-143726402-C-T is described in ClinVar as Benign. ClinVar VariationId is 263136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00651 (991/152332) while in subpopulation NFE AF = 0.0106 (724/68020). AF 95% confidence interval is 0.01. There are 8 homozygotes in GnomAd4. There are 489 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 991 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198488.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83H	NM_198488.5	MANE Select	c.3059G>A	p.Arg1020Gln	missense	Exon 5 of 5	NP_940890.4	Q6ZRV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM83H	ENST00000388913.4	TSL:5 MANE Select	c.3059G>A	p.Arg1020Gln	missense	Exon 5 of 5	ENSP00000373565.3	Q6ZRV2
FAM83H	ENST00000650760.1		c.3662G>A	p.Arg1221Gln	missense	Exon 5 of 5	ENSP00000499217.1	A0A494C1T9
FAM83H	ENST00000935286.1		c.3059G>A	p.Arg1020Gln	missense	Exon 5 of 5	ENSP00000605345.1

Frequencies

GnomAD3 genomes

AF:

0.00651

AC:

991

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00778

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00611

AC:

1373

AN:

224556

AF XY:

0.00630

show subpopulations

Gnomad AFR exome

AF:

0.00169

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.00370

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00722

GnomAD4 exome

AF:

0.00927

AC:

13474

AN:

1453362

Hom.:

Cov.:

AF XY:

0.00891

AC XY:

6437

AN XY:

722756

show subpopulations

African (AFR)

AF:

0.00162

AC:

AN:

33386

American (AMR)

AF:

0.00382

AC:

168

AN:

44030

Ashkenazi Jewish (ASJ)

AF:

0.00415

AC:

108

AN:

25994

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39480

South Asian (SAS)

AF:

0.00243

AC:

208

AN:

85486

European-Finnish (FIN)

AF:

0.00290

AC:

143

AN:

49354

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0111

AC:

12321

AN:

1109770

Other (OTH)

AF:

0.00737

AC:

443

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

949

1899

2848

3798

4747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.00651

AC:

991

AN:

152332

Hom.:

Cov.:

AF XY:

0.00656

AC XY:

489

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41580

American (AMR)

AF:

0.00777

AC:

119

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00254

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

724

AN:

68020

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00960

Hom.:

Bravo

AF:

0.00642

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00143

AC:

ESP6500EA

AF:

0.00881

AC:

ExAC

AF:

0.00590

AC:

709

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.073

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

PhyloP100

0.71

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.94

REVEL

Benign

0.089

Sift

Benign

0.54

Sift4G

Benign

0.62

Polyphen

0.15

Vest4

0.076

MVP

0.082

MPC

0.38

ClinPred

0.0059

GERP RS

3.9

Varity_R

0.063

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over