8-143726250-G-A

Variant names:

• chr8-143726250-G-A
• rs571295760
• NM_198488.5:c.3211C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_198488.5(FAM83H):​c.3211C>T​(p.Leu1071Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FAM83H NM_198488.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

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_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=3.54 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5	c.3211C>T	p.Leu1071Leu	synonymous_variant	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.3211C>T	p.Leu1071Leu	synonymous_variant	Exon 5 of 5	5	NM_198488.5	ENSP00000373565.3
FAM83H	ENST00000650760.1	c.3814C>T	p.Leu1272Leu	synonymous_variant	Exon 5 of 5			ENSP00000499217.1
FAM83H	ENST00000395103.2	n.2389C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000378535.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.85

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: rs571295760; hg19: chr8-144808420;