rs137854443

Variant names:

• chr8-143727381-C-A
• rs137854443
• NM_198488.5:c.2080G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143727381-C-A
• chr8-143727381-C-T

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.2080G>T​(p.Glu694*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000704 in 1,419,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FAM83H NM_198488.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.19

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. Fraction of 0.412 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-143727381-C-A is Pathogenic according to our data. Variant chr8-143727381-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 778.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5	c.2080G>T	p.Glu694*	stop_gained	Exon 5 of 5	ENST00000388913.4	NP_940890.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83H	ENST00000388913.4	c.2080G>T	p.Glu694*	stop_gained	Exon 5 of 5	5	NM_198488.5	ENSP00000373565.3
FAM83H	ENST00000650760.1	c.2683G>T	p.Glu895*	stop_gained	Exon 5 of 5			ENSP00000499217.1
FAM83H	ENST00000395103.2	n.1258G>T		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000378535.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1419874 Hom.: 0 Cov.: 84 AF XY: 0.00000142 AC XY: 1 AN XY: 704522

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.10e-7

Gnomad4 OTH exome AF: 0.00

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

Apr 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.83	D
Vest4		0.72
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs137854443; hg19: chr8-144809551;