Variant 8-143726250-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_198488.5(FAM83H):c.3211C>G(p.Leu1071Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,612,368 control chromosomes in the GnomAD database, including 2 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

FAM83H
NM_198488.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.54

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005820751).

BP6

Variant 8-143726250-G-C is Benign according to our data. Variant chr8-143726250-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3051740.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000722 (11/152358) while in subpopulation SAS AF= 0.00207 (10/4832). AF 95% confidence interval is 0.00112. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83H	NM_198488.5 linkuse as main transcript	c.3211C>G	p.Leu1071Val	missense_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.3211C>G	p.Leu1071Val	missense_variant	5/5	5	NM_198488.5	ENSP00000373565.3	Q6ZRV2
FAM83H	ENST00000650760.1 linkuse as main transcript	c.3814C>G	p.Leu1272Val	missense_variant	5/5			ENSP00000499217.1	A0A494C1T9
FAM83H	ENST00000395103.2 linkuse as main transcript	n.2389C>G		non_coding_transcript_exon_variant	1/2	2		ENSP00000378535.2	J3KPS2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000298

AC:

AN:

238286

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

130672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00223

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000952

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000165

AC:

241

AN:

1460010

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

177

AN XY:

726320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00269

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.000316

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FAM83H-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.0051

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.30

M_CAP

Benign

0.020

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.0

REVEL

Benign

0.11

Sift

Benign

0.24

Sift4G

Benign

0.65

Polyphen

0.0020

Vest4

0.073

MutPred

0.066

Loss of catalytic residue at L1071 (P = 0.085);

MVP

0.093

MPC

0.34

ClinPred

0.022

GERP RS

4.1

Varity_R

0.043

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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