Variant 22-36999897-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001163857.2(CIMIP4):c.577T>G(p.Ser193Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CIMIP4
NM_001163857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0110

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045760542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMIP4	NM_001163857.2 link	c.577T>G	p.Ser193Ala	missense_variant	4/6	ENST00000381821.2	NP_001157329.1	O43247-1
CIMIP4	NM_178552.4 link	c.322T>G	p.Ser108Ala	missense_variant	4/6		NP_848647.1	O43247-2
CIMIP4	XM_011530165.3 link	c.577T>G	p.Ser193Ala	missense_variant	5/7		XP_011528467.1	O43247-1
CIMIP4	XM_011530166.2 link	c.322T>G	p.Ser108Ala	missense_variant	4/6		XP_011528468.1	O43247-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEX33	ENST00000381821.2 link	c.577T>G	p.Ser193Ala	missense_variant	4/6	1	NM_001163857.2	ENSP00000371243.1	O43247-1
TEX33	ENST00000402860.7 link	c.322T>G	p.Ser108Ala	missense_variant	4/6	1		ENSP00000385179.3	O43247-2
TEX33	ENST00000405091.6 link	c.577T>G	p.Ser193Ala	missense_variant	5/7	5		ENSP00000386118.2	O43247-1
TEX33	ENST00000442538.5 link	c.151T>G	p.Ser51Ala	missense_variant	2/4	3		ENSP00000406640.1	H0Y6N4

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251392

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461720

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000182

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.577T>G (p.S193A) alteration is located in exon 4 (coding exon 3) of the TEX33 gene. This alteration results from a T to G substitution at nucleotide position 577, causing the serine (S) at amino acid position 193 to be replaced by an alanine (A). 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

Benign

0.080

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.0093

.;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.32

T;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

.;M;M

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.074

Sift

Benign

0.11

T;D;D

Sift4G

Benign

0.16

T;T;T

Polyphen

0.033

.;B;B

Vest4

0.21

MutPred

0.29

.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.014

MPC

0.044

ClinPred

0.049

GERP RS

-0.28

Varity_R

0.075

gMVP

0.040

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

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