Genetic Variant CIMIP2C:p.Thr112Lys (chr2-26576162-C-A) – 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_001322426.2(CIMIP2C):c.297C>A(p.Tyr99*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y99Y) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CIMIP2C
NM_001322426.2 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.647

Publications

3 publications found

Variant links:

Genes affected

CIMIP2C (HGNC:27938): (ciliary microtubule inner protein 2C) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CIMIP2C links:

Genome browser will be placed here

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_001322426.2. 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
	CIMIP2C	NM_001105519.3	MANE Select	c.335C>A	p.Thr112Lys	missense	Exon 2 of 4	NP_001098989.1	A6NJV1
	CIMIP2C	NM_001322426.2		c.297C>A	p.Tyr99*	stop_gained	Exon 3 of 5	NP_001309355.1	B8ZZ55

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIMIP2C	ENST00000329615.4	TSL:5 MANE Select	c.335C>A	p.Thr112Lys	missense	Exon 2 of 4	ENSP00000332875.3	A6NJV1
CIMIP2C	ENST00000409392.5	TSL:3	c.297C>A	p.Tyr99*	stop_gained	Exon 3 of 5	ENSP00000386615.1	B8ZZ55
CIMIP2C	ENST00000453368.1	TSL:3	c.36C>A	p.Tyr12*	stop_gained	Exon 1 of 4	ENSP00000395924.1	H7C0N2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248256

AF XY:

0.00

show subpopulations

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726924

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111810

Other (OTH)

AF:

0.00

AC:

AN:

60382

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.045

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.00068

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.18

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.65

PROVEAN

Benign

0.95

REVEL

Benign

0.028

Sift

Benign

0.96

Sift4G

Benign

0.94

Polyphen

0.0

Vest4

0.13

MutPred

0.29

Gain of ubiquitination at T112 (P = 0.017)

MVP

0.040

MPC

0.25

ClinPred

0.067

GERP RS

-7.9

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.025

gMVP

0.25

Mutation Taster

=160/40

disease causing (fs/PTC)

(source)

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

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