Variant rs11136321 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.2884C>T(p.Leu962=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,602,914 control chromosomes in the GnomAD database, including 441,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 31687 hom., cov: 33)

Exomes 𝑓: 0.74 ( 409335 hom. )

Consequence

FAM83H
NM_198488.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.279

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=-0.63).

BP6

Variant 8-143726577-G-A is Benign according to our data. Variant chr8-143726577-G-A is described in ClinVar as [Benign]. Clinvar id is 263135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-143726577-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.279 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM83H	NM_198488.5 linkuse as main transcript	c.2884C>T	p.Leu962=	synonymous_variant	5/5	ENST00000388913.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAM83H	ENST00000388913.4 linkuse as main transcript	c.2884C>T	p.Leu962=	synonymous_variant	5/5	5	NM_198488.5	P2
FAM83H	ENST00000650760.1 linkuse as main transcript	c.3487C>T	p.Leu1163=	synonymous_variant	5/5			A2
FAM83H	ENST00000395103.2 linkuse as main transcript	c.2065C>T	p.Leu689=	synonymous_variant, NMD_transcript_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92877

AN:

151908

Hom.:

31696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.822

Gnomad AMR

AF:

0.677

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.449

Gnomad SAS

AF:

0.684

Gnomad FIN

AF:

0.737

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.634

GnomAD3 exomes

AF:

0.677

AC:

155710

AN:

229990

Hom.:

54957

AF XY:

0.688

AC XY:

87788

AN XY:

127664

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.643

Gnomad ASJ exome

AF:

0.700

Gnomad EAS exome

AF:

0.433

Gnomad SAS exome

AF:

0.693

Gnomad FIN exome

AF:

0.729

Gnomad NFE exome

AF:

0.767

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.744

AC:

1079900

AN:

1450890

Hom.:

409335

Cov.:

AF XY:

0.743

AC XY:

536843

AN XY:

722156

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.648

Gnomad4 ASJ exome

AF:

0.705

Gnomad4 EAS exome

AF:

0.468

Gnomad4 SAS exome

AF:

0.695

Gnomad4 FIN exome

AF:

0.734

Gnomad4 NFE exome

AF:

0.780

Gnomad4 OTH exome

AF:

0.705

GnomAD4 genome

AF:

0.611

AC:

92881

AN:

152024

Hom.:

31687

Cov.:

AF XY:

0.611

AC XY:

45379

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.677

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.449

Gnomad4 SAS

AF:

0.684

Gnomad4 FIN

AF:

0.737

Gnomad4 NFE

AF:

0.771

Gnomad4 OTH

AF:

0.630

Alfa

AF:

0.719

Hom.:

13362

Bravo

AF:

0.588

EpiCase

AF:

0.756

EpiControl

AF:

0.764

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 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	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

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

-0.63

CADD

Benign

3.6

DANN

Benign

0.87

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