Genetic Variant CIMIP4:p.Arg206Gln (chr22-36999857-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001163857.2(CIMIP4):c.617G>A(p.Arg206Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R206W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CIMIP4
NM_001163857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Variant links:

Genes affected

CIMIP4 (HGNC:28568): (ciliary microtubule inner protein 4)

CIMIP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP4	NM_001163857.2 link	c.617G>A	p.Arg206Gln	missense_variant	Exon 4 of 6	ENST00000381821.2	NP_001157329.1	O43247-1
CIMIP4	NM_178552.4 link	c.362G>A	p.Arg121Gln	missense_variant	Exon 4 of 6		NP_848647.1	O43247-2
CIMIP4	XM_011530165.3 link	c.617G>A	p.Arg206Gln	missense_variant	Exon 5 of 7		XP_011528467.1	O43247-1
CIMIP4	XM_011530166.2 link	c.362G>A	p.Arg121Gln	missense_variant	Exon 4 of 6		XP_011528468.1	O43247-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEX33	ENST00000381821.2 link	c.617G>A	p.Arg206Gln	missense_variant	Exon 4 of 6	1	NM_001163857.2	ENSP00000371243.1	O43247-1
TEX33	ENST00000402860.7 link	c.362G>A	p.Arg121Gln	missense_variant	Exon 4 of 6	1		ENSP00000385179.3	O43247-2
TEX33	ENST00000405091.6 link	c.617G>A	p.Arg206Gln	missense_variant	Exon 5 of 7	5		ENSP00000386118.2	O43247-1
TEX33	ENST00000442538.5 link	c.191G>A	p.Arg64Gln	missense_variant	Exon 2 of 4	3		ENSP00000406640.1	H0Y6N4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250796

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000246

AC:

AN:

1461434

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.617G>A (p.R206Q) alteration is located in exon 4 (coding exon 3) of the TEX33 gene. This alteration results from a G to A substitution at nucleotide position 617, causing the arginine (R) at amino acid position 206 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

.;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.79

T;.;T

M_CAP

Benign

0.0077

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.9

.;L;L

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.48

Sift

Benign

0.082

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.63

MutPred

0.57

.;Loss of MoRF binding (P = 0.0716);Loss of MoRF binding (P = 0.0716);

MVP

0.10

MPC

0.085

ClinPred

0.92

GERP RS

4.9

Varity_R

0.23

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over