16-85099343-T-C

Variant names:

• chr16-85099343-T-C
• rs570833878
• NM_198491.3:c.757A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198491.3(CIBAR2):​c.757A>G​(p.Thr253Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000445 in 1,528,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.63
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008654982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.757A>G	p.Thr253Ala	missense_variant	Exon 9 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	XM_011523063.2	c.757A>G	p.Thr253Ala	missense_variant	Exon 9 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.757A>G	p.Thr253Ala	missense_variant	Exon 9 of 10		XP_016878687.1
CIBAR2	NM_001366920.1	c.754-662A>G		intron_variant	Intron 8 of 8		NP_001353849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6	c.757A>G	p.Thr253Ala	missense_variant	Exon 9 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.469-662A>G		intron_variant	Intron 6 of 6	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152056 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000108 AC: 27 AN: 250276 AF XY: 0.000126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000436

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000421 AC: 58 AN: 1376042 Hom.: 0 Cov.: 22 AF XY: 0.0000522 AC XY: 36 AN XY: 689230

African (AFR) AF: 0.00 AC: 0 AN: 31708

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25620

East Asian (EAS) AF: 0.000229 AC: 9 AN: 39286

South Asian (SAS) AF: 0.000568 AC: 48 AN: 84518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1033878

Other (OTH) AF: 0.0000174 AC: 1 AN: 57426

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152174 Hom.: 0 Cov.: 31 AF XY: 0.0000941 AC XY: 7 AN XY: 74382

African (AFR) AF: 0.0000241 AC: 1 AN: 41524

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.000148 AC: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.757A>G (p.T253A) alteration is located in exon 9 (coding exon 9) of the FAM92B gene. This alteration results from a A to G substitution at nucleotide position 757, causing the threonine (T) at amino acid position 253 to be replaced by an alanine (A). 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	0.069
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.23
DANN	Benign	0.58
DEOGEN2	Benign	0.0032	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.0087	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	.;N
PhyloP100		-1.6
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.82	N;.
REVEL	Benign	0.012
Sift	Benign	0.15	T;.
Sift4G	Benign	0.19	T;T
Polyphen		0.0020	.;B
Vest4		0.053
MutPred		0.20		Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);
MVP		0.048
MPC		0.034
ClinPred		0.021	T
GERP RS		-2.0
Varity_R		0.039
gMVP		0.038
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs570833878; hg19: chr16-85132949; COSMIC: COSV107547116;