chr19-16164850-C-G

Variant names:

• chr19-16164850-C-G
• rs112299653
• NM_054113.4:c.410G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_054113.4(CIB3):​c.410G>C​(p.Arg137Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R137W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CIB3 NM_054113.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB3	NM_054113.4	c.410G>C	p.Arg137Pro	missense_variant	Exon 5 of 6	ENST00000269878.8	NP_473454.1
CIB3	NM_001300922.2	c.263G>C	p.Arg88Pro	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.410G>C	p.Arg137Pro	missense_variant	Exon 5 of 6	1	NM_054113.4	ENSP00000269878.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		4.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.27
Sift	Benign	0.26	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.99	D;.
Vest4		0.79
MutPred		0.45		Loss of solvent accessibility (P = 0.0364);.;
MVP		0.81
MPC		0.35
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.92
gMVP		0.90
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs112299653; hg19: chr19-16275661;