19-16164903-G-C

Variant names:

• chr19-16164903-G-C
• rs765232495
• NM_054113.4:c.357C>G

Variant summary

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

The NM_054113.4(CIB3):​c.357C>G​(p.Asn119Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CIB3 NM_054113.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.87

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23803565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB3	NM_054113.4	c.357C>G	p.Asn119Lys	missense_variant	Exon 5 of 6	ENST00000269878.8	NP_473454.1
CIB3	NM_001300922.2	c.210C>G	p.Asn70Lys	missense_variant	Exon 3 of 4		NP_001287851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIB3	ENST00000269878.8	c.357C>G	p.Asn119Lys	missense_variant	Exon 5 of 6	1	NM_054113.4	ENSP00000269878.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250940 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135596

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461720 Hom.: 0 Cov.: 36 AF XY: 0.00000825 AC XY: 6 AN XY: 727160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.357C>G (p.N119K) alteration is located in exon 5 (coding exon 5) of the CIB3 gene. This alteration results from a C to G substitution at nucleotide position 357, causing the asparagine (N) at amino acid position 119 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.0010
DANN	Benign	0.71
DEOGEN2	Benign	0.23	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.047	N
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.20
Sift	Benign	0.39	T;T
Sift4G	Benign	0.89	T;T
Polyphen		0.30	B;.
Vest4		0.56
MutPred		0.44		Gain of ubiquitination at N119 (P = 0.0203);.;
MVP		0.35
MPC		0.13
ClinPred		0.26	T
GERP RS		-9.6
Varity_R		0.16
gMVP		0.69

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: rs765232495; hg19: chr19-16275714;