19-16168267-C-G

Variant names:

• chr19-16168267-C-G
• NM_054113.4:c.216G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_054113.4(CIB3):​c.216G>C​(p.Gln72His) variant causes a missense change involving the alteration of a non-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: 0.885
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB3	NM_054113.4	c.216G>C	p.Gln72His	missense_variant	Exon 4 of 6	ENST00000269878.8	NP_473454.1
CIB3	NM_001300922.2	c.69G>C	p.Gln23His	missense_variant	Exon 2 of 4		NP_001287851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIB3	ENST00000269878.8	c.216G>C	p.Gln72His	missense_variant	Exon 4 of 6	1	NM_054113.4	ENSP00000269878.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.216G>C (p.Q72H) alteration is located in exon 4 (coding exon 4) of the CIB3 gene. This alteration results from a G to C substitution at nucleotide position 216, causing the glutamine (Q) at amino acid position 72 to be replaced by a histidine (H). 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	0.000039	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.72	N;.
PhyloP100		0.89
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.10
Sift	Benign	0.030	D;D
Sift4G	Benign	0.065	T;T
Polyphen		0.40	B;.
Vest4		0.54
MutPred		0.27		Gain of disorder (P = 0.1513);.;
MVP		0.80
MPC		0.073
ClinPred		0.82	D
GERP RS		3.8
Varity_R		0.29
gMVP		0.59
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.41		Position offset: -3

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

Other links and lift over

hg19: chr19-16279078;