dbSNP rs142153660: FAM83H:p.Pro637Leu (chr8-143727551-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198488.5(FAM83H):c.1910C>T(p.Pro637Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,586,832 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 110 hom., cov: 34)

Exomes 𝑓: 0.023 ( 540 hom. )

Consequence

FAM83H
NM_198488.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.432

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=0.0016061664).

BP6

Variant 8-143727551-G-A is Benign according to our data. Variant chr8-143727551-G-A is described in ClinVar as [Benign]. Clinvar id is 263134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5 link	c.1910C>T	p.Pro637Leu	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.1910C>T	p.Pro637Leu	missense_variant	Exon 5 of 5	5	NM_198488.5	ENSP00000373565.3	Q6ZRV2
FAM83H	ENST00000650760.1 link	c.2513C>T	p.Pro838Leu	missense_variant	Exon 5 of 5			ENSP00000499217.1	A0A494C1T9
FAM83H	ENST00000395103.2 link	n.1088C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000378535.2	J3KPS2

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5041

AN:

152120

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0667

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0524

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0453

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.0541

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0246

AC:

5099

AN:

206988

Hom.:

AF XY:

0.0260

AC XY:

3010

AN XY:

115716

show subpopulations

Gnomad AFR exome

AF:

0.0672

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.0000600

Gnomad SAS exome

AF:

0.0466

Gnomad FIN exome

AF:

0.00560

Gnomad NFE exome

AF:

0.0192

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0226

AC:

32408

AN:

1434604

Hom.:

540

Cov.:

AF XY:

0.0235

AC XY:

16763

AN XY:

713182

show subpopulations

Gnomad4 AFR exome

AF:

0.0682

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.0534

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0487

Gnomad4 FIN exome

AF:

0.00715

Gnomad4 NFE exome

AF:

0.0198

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.0332

AC:

5054

AN:

152228

Hom.:

110

Cov.:

AF XY:

0.0324

AC XY:

2410

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0668

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.0524

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0455

Gnomad4 FIN

AF:

0.00621

Gnomad4 NFE

AF:

0.0189

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.0354

TwinsUK

AF:

0.0237

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.0524

AC:

158

ESP6500EA

AF:

0.0215

AC:

151

ExAC

AF:

0.0226

AC:

2574

Asia WGS

AF:

0.0190

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

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

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.10

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.9

REVEL

Benign

0.037

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Polyphen

0.42

Vest4

0.022

MPC

0.33

ClinPred

0.0092

GERP RS

3.0

Varity_R

0.088

gMVP

0.22

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