8-143728095-G-C

Position:

• chr8-143728095-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198488.5(FAM83H):​c.1366C>G​(p.Gln456Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: FAM83H NM_198488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18492615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83H	NM_198488.5	c.1366C>G	p.Gln456Glu	missense_variant	5/5	ENST00000388913.4	NP_940890.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM83H	ENST00000388913.4	c.1366C>G	p.Gln456Glu	missense_variant	5/5	5	NM_198488.5	ENSP00000373565	P2
FAM83H	ENST00000650760.1	c.1969C>G	p.Gln657Glu	missense_variant	5/5			ENSP00000499217	A2
FAM83H	ENST00000395103.2	c.547C>G	p.Gln183Glu	missense_variant, NMD_transcript_variant	1/2	2		ENSP00000378535

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.040
Eigen_PC	Benign	0.095
FATHMM_MKL	Benign	0.59	D
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.57	N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.066
Sift	Uncertain	0.028	D
Sift4G	Benign	0.32	T
Polyphen		0.26	B
Vest4		0.41
MutPred		0.36		Gain of solvent accessibility (P = 0.0411);
MVP		0.068
MPC		1.1
ClinPred		0.39	T
GERP RS		4.3
Varity_R		0.14
gMVP		0.48

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: rs387907056; hg19: chr8-144810265;