chr8-143726309-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_198488.5(FAM83H):c.3152G>A(p.Gly1051Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,611,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
FAM83H
NM_198488.5 missense
NM_198488.5 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 7.67
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2458081).
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FAM83H | NM_198488.5 | c.3152G>A | p.Gly1051Asp | 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.3152G>A | p.Gly1051Asp | missense_variant | 5/5 | 5 | NM_198488.5 | ENSP00000373565 | P2 | |
FAM83H | ENST00000650760.1 | c.3755G>A | p.Gly1252Asp | missense_variant | 5/5 | ENSP00000499217 | A2 | |||
FAM83H | ENST00000395103.2 | c.2333G>A | p.Gly778Asp | missense_variant, NMD_transcript_variant | 1/2 | 2 | ENSP00000378535 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238592Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130664
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GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459698Hom.: 0 Cov.: 83 AF XY: 0.00000689 AC XY: 5AN XY: 726110
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 06, 2023 | The c.3152G>A (p.G1051D) alteration is located in exon 5 (coding exon 4) of the FAM83H gene. This alteration results from a G to A substitution at nucleotide position 3152, causing the glycine (G) at amino acid position 1051 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at