19-16168143-T-C

Position:

• chr19-16168143-T-C

Variant summary

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

The NM_054113.4(CIB3):​c.340A>G​(p.Ile114Val) 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: CIB3 NM_054113.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

Genes affected

CIB3 (HGNC:24580): (calcium and integrin binding family member 3) This gene product shares a high degree of sequence similarity with DNA-dependent protein kinase catalytic subunit-interacting protein 2 in human and mouse, and like them may bind the catalytic subunit of DNA-dependent protein kinases. The exact function of this gene is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

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
CIB3	NM_054113.4	c.340A>G	p.Ile114Val	missense_variant	4/6	ENST00000269878.8	NP_473454.1
CIB3	NM_001300922.2	c.193A>G	p.Ile65Val	missense_variant	2/4		NP_001287851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIB3	ENST00000269878.8	c.340A>G	p.Ile114Val	missense_variant	4/6	1	NM_054113.4	ENSP00000269878	P1
CIB3	ENST00000379859.7	c.193A>G	p.Ile65Val	missense_variant	2/4	1		ENSP00000369188
CIB3	ENST00000597251.5	c.*183A>G		3_prime_UTR_variant, NMD_transcript_variant	4/6	1		ENSP00000470250
CIB3	ENST00000541493.1	n.87-3230A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

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

Sep 14, 2023

The c.340A>G (p.I114V) alteration is located in exon 4 (coding exon 4) of the CIB3 gene. This alteration results from a A to G substitution at nucleotide position 340, causing the isoleucine (I) at amino acid position 114 to be replaced by a valine (V). 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	0.28
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.78	N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.21
Sift	Benign	0.035	D;D
Sift4G	Benign	0.29	T;T
Polyphen		0.68	P;.
Vest4		0.63
MutPred		0.67		Loss of ubiquitination at K113 (P = 0.1453);.;
MVP		0.67
MPC		0.067
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.47
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-16278954;