chr8-143726309-C-T

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

Scores

2
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67
Variant links:
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]

Genome browser will be placed here

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
FAM83HNM_198488.5 linkuse as main transcriptc.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
FAM83HENST00000388913.4 linkuse as main transcriptc.3152G>A p.Gly1051Asp missense_variant 5/55 NM_198488.5 ENSP00000373565 P2
FAM83HENST00000650760.1 linkuse as main transcriptc.3755G>A p.Gly1252Asp missense_variant 5/5 ENSP00000499217 A2
FAM83HENST00000395103.2 linkuse as main transcriptc.2333G>A p.Gly778Asp missense_variant, NMD_transcript_variant 1/22 ENSP00000378535

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152214
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000419
AC:
1
AN:
238592
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
130664
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000617
AC:
9
AN:
1459698
Hom.:
0
Cov.:
83
AF XY:
0.00000689
AC XY:
5
AN XY:
726110
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152214
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsMar 06, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.79
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0097
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.21
Sift
Benign
0.22
T
Sift4G
Benign
0.32
T
Polyphen
0.99
D
Vest4
0.35
MVP
0.13
MPC
0.97
ClinPred
0.94
D
GERP RS
4.9
Varity_R
0.23
gMVP
0.35

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1319222238; hg19: chr8-144808479; API