Variant rs13254035 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198488.5(FAM83H):c.1827C>T(p.Tyr609Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 1,580,832 control chromosomes in the GnomAD database, including 722,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 56385 hom., cov: 33)

Exomes 𝑓: 0.96 ( 666043 hom. )

Consequence

FAM83H
NM_198488.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.315

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-143727634-G-A is Benign according to our data. Variant chr8-143727634-G-A is described in ClinVar as [Benign]. Clinvar id is 263133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-143727634-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.315 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.1827C>T	p.Tyr609Tyr	synonymous_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.1827C>T	p.Tyr609Tyr	synonymous_variant	5/5	5	NM_198488.5	ENSP00000373565.3	Q6ZRV2
FAM83H	ENST00000650760.1 linkuse as main transcript	c.2430C>T	p.Tyr810Tyr	synonymous_variant	5/5			ENSP00000499217.1	A0A494C1T9
FAM83H	ENST00000395103.2 linkuse as main transcript	n.1005C>T		non_coding_transcript_exon_variant	1/2	2		ENSP00000378535.2	J3KPS2

Frequencies

GnomAD3 genomes

AF:

0.832

AC:

126390

AN:

151942

Hom.:

56383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.907

Gnomad AMR

AF:

0.918

Gnomad ASJ

AF:

0.933

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.994

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.978

Gnomad OTH

AF:

0.856

GnomAD3 exomes

AF:

0.945

AC:

184387

AN:

195098

Hom.:

88402

AF XY:

0.950

AC XY:

103631

AN XY:

109084

show subpopulations

Gnomad AFR exome

AF:

0.464

Gnomad AMR exome

AF:

0.956

Gnomad ASJ exome

AF:

0.936

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.952

Gnomad FIN exome

AF:

0.995

Gnomad NFE exome

AF:

0.978

Gnomad OTH exome

AF:

0.946

GnomAD4 exome

AF:

0.962

AC:

1374726

AN:

1428782

Hom.:

666043

Cov.:

AF XY:

0.963

AC XY:

683560

AN XY:

709768

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.952

Gnomad4 ASJ exome

AF:

0.933

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.950

Gnomad4 FIN exome

AF:

0.993

Gnomad4 NFE exome

AF:

0.978

Gnomad4 OTH exome

AF:

0.939

GnomAD4 genome

AF:

0.831

AC:

126415

AN:

152050

Hom.:

56385

Cov.:

AF XY:

0.837

AC XY:

62225

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.470

Gnomad4 AMR

AF:

0.918

Gnomad4 ASJ

AF:

0.933

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.953

Gnomad4 FIN

AF:

0.994

Gnomad4 NFE

AF:

0.978

Gnomad4 OTH

AF:

0.857

Alfa

AF:

0.933

Hom.:

23104

Bravo

AF:

0.809

Asia WGS

AF:

0.943

AC:

3249

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Amelogenesis imperfecta, hypocalcification type

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Jul 28, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.74

DANN

Benign

0.94

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