6-54926527-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001010872.3(FAM83B):​c.601C>T​(p.Arg201Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000078 in 1,410,438 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R201H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

FAM83B
NM_001010872.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08
Variant links:
Genes affected
FAM83B (HGNC:21357): (family with sequence similarity 83 member B) Enables epidermal growth factor receptor binding activity; phosphatidylinositol 3-kinase binding activity; and protein kinase binding activity. Involved in cell population proliferation and epidermal growth factor receptor signaling pathway. Located in cytoplasm and membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM83BNM_001010872.3 linkc.601C>T p.Arg201Cys missense_variant Exon 3 of 5 ENST00000306858.8 NP_001010872.1 Q5T0W9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM83BENST00000306858.8 linkc.601C>T p.Arg201Cys missense_variant Exon 3 of 5 1 NM_001010872.3 ENSP00000304078.7 Q5T0W9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000447
AC:
1
AN:
223552
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
121076
show subpopulations
Gnomad AFR exome
AF:
0.0000641
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000780
AC:
11
AN:
1410438
Hom.:
0
Cov.:
30
AF XY:
0.00000429
AC XY:
3
AN XY:
699272
show subpopulations
Gnomad4 AFR exome
AF:
0.0000321
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000920
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 13, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.601C>T (p.R201C) alteration is located in exon 3 (coding exon 2) of the FAM83B gene. This alteration results from a C to T substitution at nucleotide position 601, causing the arginine (R) at amino acid position 201 to be replaced by a cysteine (C). 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
Benign
0.24
BayesDel_addAF
Uncertain
0.025
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.70
D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.14
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.031
D
Polyphen
1.0
D
Vest4
0.59
MutPred
0.67
Loss of MoRF binding (P = 0.0054);
MVP
0.62
MPC
0.36
ClinPred
0.99
D
GERP RS
4.4
Varity_R
0.60
gMVP
0.56

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: rs1484573093; hg19: chr6-54791325; API