rs7821494

Positions:

• chr8-143729461-C-G
• chr8-143729461-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198488.5(FAM83H):​c.448-138G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 938,528 control chromosomes in the GnomAD database, including 27,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4895 hom., cov: 32)
  • Exomes 𝑓: 0.23 (22423 hom.)
• Consequence: FAM83H NM_198488.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.372

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-143729461-C-G is Benign according to our data. Variant chr8-143729461-C-G is described in ClinVar as [Benign]. Clinvar id is 1279352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83H	NM_198488.5	c.448-138G>C		intron_variant		ENST00000388913.4	NP_940890.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM83H	ENST00000388913.4	c.448-138G>C		intron_variant		5	NM_198488.5	ENSP00000373565.3
FAM83H	ENST00000650760.1	c.1051-138G>C		intron_variant				ENSP00000499217.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37226 AN: 151900 Hom.: 4883 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.225 AC: 177087 AN: 786510 Hom.: 22423 AF XY: 0.226 AC XY: 92072 AN XY: 406510

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.245 AC: 37275 AN: 152018 Hom.: 4895 Cov.: 32 AF XY: 0.250 AC XY: 18559 AN XY: 74292

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.249

Alfa AF: 0.124 Hom.: 214

Bravo AF: 0.249

Asia WGS AF: 0.399 AC: 1385 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.62

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: rs7821494; hg19: chr8-144811631;