Genetic Variant NM_198491.3:c.629A>G (chr16-85102236-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198491.3(CIBAR2):c.629A>G(p.Tyr210Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000688 in 1,454,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

CIBAR2
NM_198491.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

Publications

0 publications found

Variant links:

Genes affected

CIBAR2 (HGNC:24781): (CBY1 interacting BAR domain containing 2) Predicted to be involved in cilium assembly. Predicted to be located in centriole and cytoplasm. Predicted to be active in ciliary basal body and ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

CIBAR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
CIBAR2	NM_198491.3 link	c.629A>G	p.Tyr210Cys	missense_variant	Exon 7 of 9	ENST00000539556.6	NP_940893.1	Q6ZTR7A0A1X7SC74
CIBAR2	NM_001366920.1 link	c.629A>G	p.Tyr210Cys	missense_variant	Exon 7 of 9		NP_001353849.1
CIBAR2	XM_011523063.2 link	c.629A>G	p.Tyr210Cys	missense_variant	Exon 7 of 10		XP_011521365.1	Q6ZTR7A0A1X7SC74
CIBAR2	XM_017023198.2 link	c.629A>G	p.Tyr210Cys	missense_variant	Exon 7 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6 link	c.629A>G	p.Tyr210Cys	missense_variant	Exon 7 of 9	5	NM_198491.3	ENSP00000443411.1		A0A1X7SC74
CIBAR2	ENST00000618669.3 link	c.344A>G	p.Tyr115Cys	missense_variant	Exon 5 of 7	5		ENSP00000478373.1		A0A087WU51

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000688

AC:

AN:

1454152

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33318

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000905

AC:

AN:

1104946

Other (OTH)

AF:

0.00

AC:

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.629A>G (p.Y210C) alteration is located in exon 7 (coding exon 7) of the FAM92B gene. This alteration results from a A to G substitution at nucleotide position 629, causing the tyrosine (Y) at amino acid position 210 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0099

.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

.;M

PhyloP100

2.4

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.13

Sift

Benign

0.046

D;.

Sift4G

Benign

0.066

T;T

Polyphen

0.11

.;B

Vest4

0.67

MutPred

0.46

Gain of methylation at K209 (P = 0.0159);Gain of methylation at K209 (P = 0.0159);

MVP

0.27

MPC

0.077

ClinPred

0.32

GERP RS

4.6

Varity_R

0.10

gMVP

0.29

Mutation Taster

=89/11

polymorphism

(source)

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

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NM_198491.3:c.629A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over