Variant rs137854442 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_198488.5(FAM83H):c.860C>T(p.Ser287Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,608,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FAM83H
NM_198488.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1405631).

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00000893 (13/1455934) while in subpopulation AMR AF= 0.000114 (5/44042). AF 95% confidence interval is 0.0000441. There are 0 homozygotes in gnomad4_exome. There are 10 alleles in male gnomad4_exome subpopulation. Median coverage is 38. This position pass quality control queck.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83H	NM_198488.5 linkuse as main transcript	c.860C>T	p.Ser287Leu	missense_variant	5/5	ENST00000388913.4	NP_940890.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FAM83H	ENST00000388913.4 linkuse as main transcript	c.860C>T	p.Ser287Leu	missense_variant	5/5	5	NM_198488.5	ENSP00000373565	P2
FAM83H	ENST00000650760.1 linkuse as main transcript	c.1463C>T	p.Ser488Leu	missense_variant	5/5			ENSP00000499217	A2
FAM83H	ENST00000395103.2 linkuse as main transcript	c.41C>T	p.Ser14Leu	missense_variant, NMD_transcript_variant	1/2	2		ENSP00000378535

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152160

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000212

AC:

AN:

235646

Hom.:

AF XY:

0.0000231

AC XY:

AN XY:

129590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000885

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000952

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.00000893

AC:

AN:

1455934

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

724164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74468

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000688

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Benign

-0.0041

Eigen_PC

Benign

0.066

FATHMM_MKL

Benign

0.66

M_CAP

Benign

0.027

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.042

Sift

Benign

0.13

Sift4G

Uncertain

0.026

Polyphen

0.82

Vest4

0.18

MutPred

0.42

Loss of glycosylation at S287 (P = 0.0225);

MVP

0.043

MPC

0.41

ClinPred

0.44

GERP RS

4.8

Varity_R

0.21

gMVP

0.64

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over