rs796065022

Positions:

• chr8-143727587-AGG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_198488.5(FAM83H):​c.1872_1873del​(p.Leu625AlafsTer79) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: FAM83H NM_198488.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.42

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-143727587-AGG-A is Pathogenic according to our data. Variant chr8-143727587-AGG-A is described in ClinVar as [Pathogenic]. Clinvar id is 779.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM83H	NM_198488.5	c.1872_1873del	p.Leu625AlafsTer79	frameshift_variant	5/5	ENST00000388913.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM83H	ENST00000388913.4	c.1872_1873del	p.Leu625AlafsTer79	frameshift_variant	5/5	5	NM_198488.5	P2
FAM83H	ENST00000650760.1	c.2475_2476del	p.Leu826AlafsTer79	frameshift_variant	5/5			A2
FAM83H	ENST00000395103.2	c.1052_1053del	p.Leu352AlafsTer79	frameshift_variant, NMD_transcript_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Amelogenesis imperfecta, type 3A Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs796065022; hg19: chr8-144809757;