8-93701333-G-A

Position:

• chr8-93701333-G-A

Variant summary

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

The NM_145269.5(CIBAR1):​c.136G>A​(p.Asp46Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 10.0

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.136G>A	p.Asp46Asn	missense_variant	2/9	ENST00000518322.6	NP_660312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6	c.136G>A	p.Asp46Asn	missense_variant	2/9	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

Jan 09, 2024

The c.136G>A (p.D46N) alteration is located in exon 2 (coding exon 2) of the FAM92A1 gene. This alteration results from a G to A substitution at nucleotide position 136, causing the aspartic acid (D) at amino acid position 46 to be replaced by an asparagine (N). 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	Pathogenic	0.94
BayesDel_addAF	Benign	-0.0029	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T;.;T;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.70	D;D;D;D;D
MetaSVM	Benign	-0.29	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.4	D;D;D;D;.
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D;D;D;D;.
Sift4G	Uncertain	0.024	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.82
MutPred		0.67		Gain of MoRF binding (P = 0.0343);Gain of MoRF binding (P = 0.0343);Gain of MoRF binding (P = 0.0343);Gain of MoRF binding (P = 0.0343);Gain of MoRF binding (P = 0.0343);
MVP		0.79
MPC		0.61
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.84
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-94713561;