chr8-143726402-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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 -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 id is 263136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-143726402-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 991 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5 link	c.3059G>A	p.Arg1020Gln	missense_variant	Exon 5 of 5	ENST00000388913.4	NP_940890.4	Q6ZRV2Q71RB4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM83H	ENST00000388913.4 link	c.3059G>A	p.Arg1020Gln	missense_variant	Exon 5 of 5	5	NM_198488.5	ENSP00000373565.3	Q6ZRV2
FAM83H	ENST00000650760.1 link	c.3662G>A	p.Arg1221Gln	missense_variant	Exon 5 of 5			ENSP00000499217.1	A0A494C1T9
FAM83H	ENST00000395103.2 link	n.2237G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000378535.2	J3KPS2

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

GnomAD3 exomes

AF:

0.00611

AC:

1373

AN:

224556

Hom.:

AF XY:

0.00630

AC XY:

781

AN XY:

124012

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 SAS exome

AF:

0.00238

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

Gnomad4 AFR exome

AF:

0.00162

Gnomad4 AMR exome

AF:

0.00382

Gnomad4 ASJ exome

AF:

0.00415

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00243

Gnomad4 FIN exome

AF:

0.00290

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00737

GnomAD4 genome

AF:

0.00651

AC:

991

AN:

152332

Hom.:

Cov.:

AF XY:

0.00656

AC XY:

489

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00777

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00961

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

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

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

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