16-66934352-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016062.4(CIAO2B):​c.13G>A​(p.Gly5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,565,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CIAO2B
NM_016062.4 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
Variant links:
Genes affected
CIAO2B (HGNC:24261): (cytosolic iron-sulfur assembly component 2B) Involved in chromosome segregation; iron-sulfur cluster assembly; and protein maturation by iron-sulfur cluster transfer. Located in cytosol; nucleoplasm; and spindle. Part of CIA complex and MMXD complex. [provided by Alliance of Genome Resources, Apr 2022]
CES2 (HGNC:1864): (carboxylesterase 2) This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. The protein encoded by this gene is the major intestinal enzyme and functions in intestine drug clearance. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.050544232).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CIAO2BNM_016062.4 linkc.13G>A p.Gly5Ser missense_variant Exon 1 of 5 ENST00000422424.7 NP_057146.1 Q9Y3D0
CIAO2BNR_024525.3 linkn.51G>A non_coding_transcript_exon_variant Exon 1 of 4
CIAO2BNR_046109.2 linkn.51G>A non_coding_transcript_exon_variant Exon 1 of 5
CES2NM_003869.6 linkc.-1284C>T upstream_gene_variant NP_003860.3 O00748-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CIAO2BENST00000422424.7 linkc.13G>A p.Gly5Ser missense_variant Exon 1 of 5 1 NM_016062.4 ENSP00000387471.2 Q9Y3D0

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152242
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000861
AC:
15
AN:
174132
Hom.:
0
AF XY:
0.000113
AC XY:
11
AN XY:
97020
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000194
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000160
AC:
226
AN:
1413276
Hom.:
0
Cov.:
31
AF XY:
0.000143
AC XY:
100
AN XY:
700806
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000202
Gnomad4 OTH exome
AF:
0.0000850
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000118
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000941
AC:
11

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.13G>A (p.G5S) alteration is located in exon 1 (coding exon 1) of the FAM96B gene. This alteration results from a G to A substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 to be replaced by a serine (S). 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
0.10
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.016
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.051
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.45
T
PROVEAN
Benign
0.050
N
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.056
T
Polyphen
0.0
B
Vest4
0.26
MutPred
0.30
Gain of glycosylation at G5 (P = 0.0023);
MVP
0.22
MPC
0.47
ClinPred
0.21
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2
Varity_R
0.42
gMVP
0.54

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: rs746181958; hg19: chr16-66968255; API