19-16164886-G-C

Variant names:

• chr19-16164886-G-C
• rs773279506
• NM_054113.4:c.374C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_054113.4(CIB3):​c.374C>G​(p.Ala125Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. A125V) 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: 3.64
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23457766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB3	NM_054113.4	c.374C>G	p.Ala125Gly	missense_variant	Exon 5 of 6	ENST00000269878.8	NP_473454.1
CIB3	NM_001300922.2	c.227C>G	p.Ala76Gly	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.374C>G	p.Ala125Gly	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	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.85	D;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		3.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.21
Sift	Benign	0.39	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.055	B;.
Vest4		0.31
MutPred		0.55		Loss of catalytic residue at A125 (P = 0.0091);.;
MVP		0.64
MPC		0.059
ClinPred		0.52	D
GERP RS		-0.60
Varity_R		0.13
gMVP		0.47
Mutation Taster		=88/12	polymorphism

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: rs773279506; hg19: chr19-16275697;