Genetic Variant NM_054113.4:c.112G>A (chr19-16169716-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_054113.4(CIB3):c.112G>A(p.Ala38Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CIB3
NM_054113.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74

Publications

0 publications found

Variant links:

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]

CIB3 links:

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ACMG classification

Classification was made for transcript

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.112G>A	p.Ala38Thr	missense	Exon 3 of 6	NP_473454.1	Q96Q77-1
	CIB3	NM_001300922.2		c.52-1432G>A		intron	N/A	NP_001287851.1	Q96Q77-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIB3	ENST00000269878.8	TSL:1 MANE Select	c.112G>A	p.Ala38Thr	missense	Exon 3 of 6	ENSP00000269878.3	Q96Q77-1
CIB3	ENST00000379859.7	TSL:1	c.52-1432G>A		intron	N/A	ENSP00000369188.3	Q96Q77-2
CIB3	ENST00000597251.5	TSL:1	n.93G>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000470250.1	M0QZ29

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248022

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

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

AF:

6.85e-7

AC:

AN:

1459710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33412

American (AMR)

AF:

0.0000225

AC:

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25972

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.00

AC:

AN:

86084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110922

Other (OTH)

AF:

0.00

AC:

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.5

PhyloP100

7.7

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.1

REVEL

Benign

0.17

Sift

Benign

0.43

Sift4G

Benign

0.59

Polyphen

0.82

Vest4

0.85

MutPred

0.43

Gain of phosphorylation at A38 (P = 0.0716)

MVP

0.76

MPC

0.30

ClinPred

0.97

GERP RS

4.9

Varity_R

0.22

gMVP

0.61

Mutation Taster

=21/79

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over