Variant 22-36999894-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001163857.2(TEX33):c.580G>A(p.Val194Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TEX33
NM_001163857.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.303

Variant links:

Genes affected

TEX33 (HGNC:):

TEX33 links:

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01222226).

BP6

Variant 22-36999894-C-T is Benign according to our data. Variant chr22-36999894-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2471283.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TEX33	NM_001163857.2 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	4/6	ENST00000381821.2	NP_001157329.1
TEX33	NM_178552.4 linkuse as main transcript	c.325G>A	p.Val109Ile	missense_variant	4/6		NP_848647.1
TEX33	XM_011530165.3 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	5/7		XP_011528467.1
TEX33	XM_011530166.2 linkuse as main transcript	c.325G>A	p.Val109Ile	missense_variant	4/6		XP_011528468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIMIP4	ENST00000381821.2 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	4/6	1	NM_001163857.2	ENSP00000371243	P2	O43247-1
CIMIP4	ENST00000402860.7 linkuse as main transcript	c.325G>A	p.Val109Ile	missense_variant	4/6	1		ENSP00000385179	A2	O43247-2
CIMIP4	ENST00000405091.6 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	5/7	5		ENSP00000386118	P2	O43247-1
CIMIP4	ENST00000442538.5 linkuse as main transcript	c.157G>A	p.Val53Ile	missense_variant	2/4	3		ENSP00000406640

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000159

AC:

AN:

251382

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000131

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

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.20

DANN

Benign

0.34

DEOGEN2

Benign

0.00099

.;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.39

T;.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.5

.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.24

N;N;N

REVEL

Benign

0.026

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.73

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.077

MVP

0.014

MPC

0.027

ClinPred

0.027

GERP RS

-0.82

Varity_R

0.023

gMVP

0.029

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