8-93704943-G-C

Variant names:

• chr8-93704943-G-C
• rs761322248
• NM_145269.5:c.365G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145269.5(CIBAR1):​c.365G>C​(p.Arg122Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.95

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR1	NM_145269.5	c.365G>C	p.Arg122Pro	missense_variant	Exon 4 of 9	ENST00000518322.6	NP_660312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6	c.365G>C	p.Arg122Pro	missense_variant	Exon 4 of 9	5	NM_145269.5	ENSP00000429367.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;T;.;T;.;T;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.79	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.38	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;D;.;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.010	D;D;D;D;D;D;.;D;D
Sift4G	Uncertain	0.023	D;D;D;D;D;D;D;D;D
Polyphen		1.0	.;.;D;.;.;.;.;.;.
Vest4		0.92, 0.77, 0.90, 0.90
MutPred		0.61		.;.;Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);.;Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);.;.;
MVP		0.86
MPC		0.70
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.80
gMVP		0.87

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

Other links and lift over

dbSNP: rs761322248; hg19: chr8-94717171;