8-93726419-C-T

Position:

• chr8-93726419-C-T

Variant summary

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

The NM_145269.5(CIBAR1):​c.683C>T​(p.Pro228Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.739

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIBAR1	NM_145269.5	c.683C>T	p.Pro228Leu	missense_variant	8/9	ENST00000518322.6	NP_660312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6	c.683C>T	p.Pro228Leu	missense_variant	8/9	5	NM_145269.5	ENSP00000429367	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.683C>T (p.P228L) alteration is located in exon 8 (coding exon 8) of the FAM92A1 gene. This alteration results from a C to T substitution at nucleotide position 683, causing the proline (P) at amino acid position 228 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	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.055	T;.;T;.;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D;D;D;.;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T;T;T;T;T;T
MetaSVM	Benign	-0.39	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.8	D;N;.;D;D;D
REVEL	Benign	0.079
Sift	Benign	0.16	T;T;.;T;T;T
Sift4G	Benign	0.17	T;D;T;T;T;D
Polyphen		0.0010	B;B;.;.;.;.
Vest4		0.22
MutPred		0.37		Loss of loop (P = 0.0288);.;.;.;.;.;
MVP		0.30
MPC		0.14
ClinPred		0.26	T
GERP RS		-1.2
Varity_R		0.069
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.33		Position offset: -25

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

Publications

LitVar

Other links and lift over

dbSNP: rs1004631431; hg19: chr8-94738647;