Variant 22-37001928-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000381821.2(TEX33):c.398C>T(p.Thr133Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,613,658 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

TEX33
ENST00000381821.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0890

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011184692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMIP4	NM_001163857.2 linkuse as main transcript	c.398C>T	p.Thr133Met	missense_variant	3/6	ENST00000381821.2	NP_001157329.1	O43247-1
CIMIP4	NM_178552.4 linkuse as main transcript	c.143C>T	p.Thr48Met	missense_variant	3/6		NP_848647.1	O43247-2
CIMIP4	XM_011530165.3 linkuse as main transcript	c.398C>T	p.Thr133Met	missense_variant	4/7		XP_011528467.1	O43247-1
CIMIP4	XM_011530166.2 linkuse as main transcript	c.143C>T	p.Thr48Met	missense_variant	3/6		XP_011528468.1	O43247-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEX33	ENST00000381821.2 linkuse as main transcript	c.398C>T	p.Thr133Met	missense_variant	3/6	1	NM_001163857.2	ENSP00000371243.1	O43247-1
TEX33	ENST00000402860.7 linkuse as main transcript	c.143C>T	p.Thr48Met	missense_variant	3/6	1		ENSP00000385179.3	O43247-2
TEX33	ENST00000405091.6 linkuse as main transcript	c.398C>T	p.Thr133Met	missense_variant	4/7	5		ENSP00000386118.2	O43247-1
TEX33	ENST00000442538.5 linkuse as main transcript	c.63+265C>T		intron_variant		3		ENSP00000406640.1	H0Y6N4

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000332

AC:

AN:

250168

Hom.:

AF XY:

0.000340

AC XY:

AN XY:

135160

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.000697

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000395

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000336

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000224

AC:

328

AN:

1461376

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000360

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000348

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000249

Hom.:

Bravo

AF:

0.000374

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000305

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000535

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

Aug 13, 2021

The c.398C>T (p.T133M) alteration is located in exon 3 (coding exon 2) of the TEX33 gene. This alteration results from a C to T substitution at nucleotide position 398, causing the threonine (T) at amino acid position 133 to be replaced by a methionine (M). 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

0.072

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.1

DANN

Benign

0.79

DEOGEN2

Benign

0.0024

.;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.30

T;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.73

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.067

.;B;B

Vest4

0.065

MVP

0.014

MPC

0.21

ClinPred

0.014

GERP RS

-7.3

Varity_R

0.013

gMVP

0.068

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