Genetic Variant TEX35:p.His176Arg (chr1-178520858-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032126.5(TEX35):c.527A>G(p.His176Arg) 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 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TEX35
NM_032126.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.778

Publications

0 publications found

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017752677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5 link	c.527A>G	p.His176Arg	missense_variant	Exon 7 of 9	ENST00000319416.7	NP_115502.2	Q5T0J7-1
TEX35	NM_001170722.2 link	c.551A>G	p.His184Arg	missense_variant	Exon 7 of 9		NP_001164193.1	Q5T0J7-2
TEX35	NM_001170723.2 link	c.527A>G	p.His176Arg	missense_variant	Exon 7 of 9		NP_001164194.1	Q5T0J7-5
TEX35	NM_001170724.2 link	c.527A>G	p.His176Arg	missense_variant	Exon 7 of 9		NP_001164195.1	Q5T0J7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX35	ENST00000319416.7 link	c.527A>G	p.His176Arg	missense_variant	Exon 7 of 9	1	NM_032126.5	ENSP00000323795.2		Q5T0J7-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000279

AC:

AN:

251328

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00

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:

0.00000342

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112004

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000138

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41558

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

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:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.000110

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

Dec 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.527A>G (p.H176R) alteration is located in exon 7 (coding exon 7) of the TEX35 gene. This alteration results from a A to G substitution at nucleotide position 527, causing the histidine (H) at amino acid position 176 to be replaced by an arginine (R). 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

-0.69

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.0051

T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.25

T;T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;N;.

PhyloP100

0.78

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.50

N;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.084

T;T;T;T

Sift4G

Benign

0.077

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.11

MVP

0.014

MPC

0.099

ClinPred

0.021

GERP RS

-2.7

PromoterAI

0.066

Neutral

(source)

Varity_R

0.046

gMVP

0.0097

Mutation Taster

=99/1

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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1-178520858-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over