19-16168179-C-T

Variant names:

• chr19-16168179-C-T
• rs372985211
• NM_054113.4:c.304G>A

Variant summary

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

The NM_054113.4(CIB3):​c.304G>A​(p.Ala102Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A102P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIB3 NM_054113.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.70
• 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054113.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB3	NM_054113.4	MANE Select	c.304G>A	p.Ala102Thr	missense	Exon 4 of 6	NP_473454.1	Q96Q77-1
	CIB3	NM_001300922.2		c.157G>A	p.Ala53Thr	missense	Exon 2 of 4	NP_001287851.1	Q96Q77-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB3	ENST00000269878.8	TSL:1 MANE Select	c.304G>A	p.Ala102Thr	missense	Exon 4 of 6	ENSP00000269878.3	Q96Q77-1
	CIB3	ENST00000379859.7	TSL:1	c.157G>A	p.Ala53Thr	missense	Exon 2 of 4	ENSP00000369188.3	Q96Q77-2
	CIB3	ENST00000597251.5	TSL:1	n.*147G>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000470250.1	M0QZ29

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.7
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.16	T
Polyphen		0.98	D
Vest4		0.68
MutPred		0.38		Gain of phosphorylation at A102 (P = 0.027)
MVP		0.79
MPC		0.24
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.74
gMVP		0.75
Mutation Taster		=40/60	disease causing

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

Other links and lift over

dbSNP: rs372985211; hg19: chr19-16278990; COSMIC: COSV54165882;