19-16168272-G-T

Variant names:

• chr19-16168272-G-T
• rs767528190
• NM_054113.4:c.211C>A

Variant summary

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

The NM_054113.4(CIB3):​c.211C>A​(p.Arg71Ser) 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. R71C) 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: 5.41
• Publications: 3 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, 0.802

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.211C>A	p.Arg71Ser	missense	Exon 4 of 6	NP_473454.1	Q96Q77-1
	CIB3	NM_001300922.2		c.64C>A	p.Arg22Ser	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.211C>A	p.Arg71Ser	missense	Exon 4 of 6	ENSP00000269878.3	Q96Q77-1
	CIB3	ENST00000379859.7	TSL:1	c.64C>A	p.Arg22Ser	missense	Exon 2 of 4	ENSP00000369188.3	Q96Q77-2
	CIB3	ENST00000597251.5	TSL:1	n.*54C>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000470250.1	M0QZ29

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250134 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.18
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.037	D
Polyphen		0.88	P
Vest4		0.85
MutPred		0.54		Loss of catalytic residue at R71 (P = 0.0598)
MVP		0.81
MPC		0.13
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.73
gMVP		0.70
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs767528190; hg19: chr19-16279083; COSMIC: COSV54165469;