16-85100221-T-A

Variant names:

• chr16-85100221-T-A
• rs1370956718
• NM_198491.3:c.671A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198491.3(CIBAR2):​c.671A>T​(p.Gln224Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.95

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11143687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.671A>T	p.Gln224Leu	missense_variant	Exon 8 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	NM_001366920.1	c.671A>T	p.Gln224Leu	missense_variant	Exon 8 of 9		NP_001353849.1
CIBAR2	XM_011523063.2	c.671A>T	p.Gln224Leu	missense_variant	Exon 8 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.671A>T	p.Gln224Leu	missense_variant	Exon 8 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6	c.671A>T	p.Gln224Leu	missense_variant	Exon 8 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.386A>T	p.Gln129Leu	missense_variant	Exon 6 of 7	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000819 AC: 2 AN: 244220 Hom.: 0 AF XY: 0.0000151 AC XY: 2 AN XY: 132054

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: 0.0000691

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457518 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724698

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: 0.0000354

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.671A>T (p.Q224L) alteration is located in exon 8 (coding exon 8) of the FAM92B gene. This alteration results from a A to T substitution at nucleotide position 671, causing the glutamine (Q) at amino acid position 224 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.16
DANN	Benign	0.61
DEOGEN2	Benign	0.0088	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.015
Sift	Benign	0.34	T;.
Sift4G	Benign	0.37	T;T
Polyphen		0.0020	.;B
Vest4		0.34
MutPred		0.32		Loss of phosphorylation at Y227 (P = 0.11);Loss of phosphorylation at Y227 (P = 0.11);
MVP		0.048
MPC		0.035
ClinPred		0.052	T
GERP RS		-8.0
Varity_R		0.060
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1370956718; hg19: chr16-85133827;