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GeneBe

8-143726269-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_198488.5(FAM83H):c.3192G>A(p.Pro1064=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,612,136 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 31 hom., cov: 34)
Exomes 𝑓: 0.0011 ( 35 hom. )

Consequence

FAM83H
NM_198488.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-143726269-C-T is Benign according to our data. Variant chr8-143726269-C-T is described in ClinVar as [Benign]. Clinvar id is 792113.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.5 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1680/152290) while in subpopulation AFR AF= 0.0379 (1577/41562). AF 95% confidence interval is 0.0364. There are 31 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1676 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAM83HNM_198488.5 linkuse as main transcriptc.3192G>A p.Pro1064= synonymous_variant 5/5 ENST00000388913.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAM83HENST00000388913.4 linkuse as main transcriptc.3192G>A p.Pro1064= synonymous_variant 5/55 NM_198488.5 P2
FAM83HENST00000650760.1 linkuse as main transcriptc.3795G>A p.Pro1265= synonymous_variant 5/5 A2
FAM83HENST00000395103.2 linkuse as main transcriptc.2373G>A p.Pro791= synonymous_variant, NMD_transcript_variant 1/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1676
AN:
152172
Hom.:
31
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0379
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00484
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00271
AC:
642
AN:
237310
Hom.:
11
AF XY:
0.00181
AC XY:
236
AN XY:
130204
show subpopulations
Gnomad AFR exome
AF:
0.0392
Gnomad AMR exome
AF:
0.00196
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000574
Gnomad OTH exome
AF:
0.00189
GnomAD4 exome
AF:
0.00112
AC:
1636
AN:
1459846
Hom.:
35
Cov.:
83
AF XY:
0.000924
AC XY:
671
AN XY:
726246
show subpopulations
Gnomad4 AFR exome
AF:
0.0405
Gnomad4 AMR exome
AF:
0.00224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.00232
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1680
AN:
152290
Hom.:
31
Cov.:
34
AF XY:
0.00987
AC XY:
735
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0379
Gnomad4 AMR
AF:
0.00477
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00992
Alfa
AF:
0.00330
Hom.:
2
Bravo
AF:
0.0127
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.0000594

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
0.13
Dann
Benign
0.90

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: rs77431583; hg19: chr8-144808439; API