Variant 8-93701312-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_145269.5(CIBAR1):c.115C>T(p.Arg39Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CIBAR1
NM_145269.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

Variant links:

Genes affected

CIBAR1 (HGNC:30452): (CBY1 interacting BAR domain containing 1) Enables phospholipid binding activity. Involved in several processes, including inner mitochondrial membrane organization; limb morphogenesis; and membrane tubulation. Located in several cellular components, including centriole; ciliary base; and mitochondrial crista. [provided by Alliance of Genome Resources, Apr 2022]

CIBAR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.928

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR1	NM_145269.5 link	c.115C>T	p.Arg39Trp	missense_variant	Exon 2 of 9	ENST00000518322.6	NP_660312.2	A1XBS5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6 link	c.115C>T	p.Arg39Trp	missense_variant	Exon 2 of 9	5	NM_145269.5	ENSP00000429367.1		A1XBS5-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00000804

AC:

AN:

248884

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.0000647

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:

0.000165

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461580

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727054

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:

0.0000189

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.115C>T (p.R39W) alteration is located in exon 2 (coding exon 2) of the FAM92A1 gene. This alteration results from a C to T substitution at nucleotide position 115, causing the arginine (R) at amino acid position 39 to be replaced by a tryptophan (W). 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

0.97

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.;T;.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.052

MetaRNN

Pathogenic

0.93

D;D;D;D;D

MetaSVM

Benign

-0.47

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-6.3

D;D;D;D;.

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D;D;D;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

0.41

B;.;.;.;.

Vest4

0.86

MutPred

0.85

Loss of MoRF binding (P = 0.0488);Loss of MoRF binding (P = 0.0488);Loss of MoRF binding (P = 0.0488);Loss of MoRF binding (P = 0.0488);Loss of MoRF binding (P = 0.0488);

MVP

0.81

MPC

0.16

ClinPred

0.98

GERP RS

3.5

Varity_R

0.76

gMVP

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over