8-93728215-G-T

Position:

• chr8-93728215-G-T

Variant summary

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

The NM_145269.5(CIBAR1):​c.788G>T​(p.Cys263Phe) 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. 13/20 in silico tools predict 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: 0.905

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]

RBM12B (HGNC:32310): (RNA binding motif protein 12B) Enables RNA binding activity. Predicted to be involved in regulation of RNA splicing. Predicted to be part of ribonucleoprotein complex. Predicted to be active in nucleoplasm. [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=0.1612744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIBAR1	NM_145269.5	c.788G>T	p.Cys263Phe	missense_variant	9/9	ENST00000518322.6	NP_660312.2
RBM12B	NM_001377960.1	c.*5190C>A		3_prime_UTR_variant	4/4	ENST00000520560.6	NP_001364889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6	c.788G>T	p.Cys263Phe	missense_variant	9/9	5	NM_145269.5	ENSP00000429367	P1
RBM12B	ENST00000520560.6	c.*5190C>A		3_prime_UTR_variant	4/4	2	NM_001377960.1	ENSP00000429807	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Mar 31, 2023

The c.788G>T (p.C263F) alteration is located in exon 9 (coding exon 9) of the FAM92A1 gene. This alteration results from a G to T substitution at nucleotide position 788, causing the cysteine (C) at amino acid position 263 to be replaced by a phenylalanine (F). 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	0.097
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0078	T;.;T;.;.
Eigen	Benign	0.073
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.82	T;T;T;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.84	N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	D;D;.;D;D
REVEL	Benign	0.046
Sift	Benign	0.11	T;D;.;T;T
Sift4G	Benign	0.069	T;D;T;T;T
Polyphen		0.62	P;P;.;.;.
Vest4		0.18
MutPred		0.24		Gain of sheet (P = 0.039);.;.;.;.;
MVP		0.42
MPC		0.35
ClinPred		0.56	D
GERP RS		2.5
Varity_R		0.12
gMVP		0.095

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-94740443;