Genetic Variant TEX35:p.Glu58Gln (chr1-178515871-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032126.5(TEX35):c.172G>C(p.Glu58Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,612,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TEX35
NM_032126.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

TEX35 (HGNC:25366): (testis expressed 35) Located in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

TEX35 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1650474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5 link	c.172G>C	p.Glu58Gln	missense_variant	Exon 4 of 9	ENST00000319416.7	NP_115502.2	Q5T0J7-1
TEX35	NM_001170722.2 link	c.196G>C	p.Glu66Gln	missense_variant	Exon 4 of 9		NP_001164193.1	Q5T0J7-2
TEX35	NM_001170723.2 link	c.172G>C	p.Glu58Gln	missense_variant	Exon 4 of 9		NP_001164194.1	Q5T0J7-5
TEX35	NM_001170724.2 link	c.172G>C	p.Glu58Gln	missense_variant	Exon 4 of 9		NP_001164195.1	Q5T0J7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX35	ENST00000319416.7 link	c.172G>C	p.Glu58Gln	missense_variant	Exon 4 of 9	1	NM_032126.5	ENSP00000323795.2		Q5T0J7-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000281

AC:

AN:

249206

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.000374

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000685

AC:

AN:

1459908

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726136

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33452

American (AMR)

AF:

0.0000224

AC:

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

85896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110768

Other (OTH)

AF:

0.0000166

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41536

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.172G>C (p.E58Q) alteration is located in exon 4 (coding exon 4) of the TEX35 gene. This alteration results from a G to C substitution at nucleotide position 172, causing the glutamic acid (E) at amino acid position 58 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

Benign

0.31

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

T;.;.;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.0

L;L;L;.

PhyloP100

2.1

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.062

T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.24

MVP

0.25

MPC

0.44

ClinPred

0.22

GERP RS

5.4

Varity_R

0.17

gMVP

0.053

Mutation Taster

=277/23

polymorphism

(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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1-178515871-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over