Genetic Variant TEX35:p.Phe81Cys (chr1-178516640-T-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_032126.5(TEX35):c.242T>G(p.Phe81Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,613,786 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 1 hom. )

Consequence

TEX35
NM_032126.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38763916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5 link	c.242T>G	p.Phe81Cys	missense_variant	Exon 5 of 9	ENST00000319416.7	NP_115502.2	Q5T0J7-1
TEX35	NM_001170722.2 link	c.266T>G	p.Phe89Cys	missense_variant	Exon 5 of 9		NP_001164193.1	Q5T0J7-2
TEX35	NM_001170723.2 link	c.242T>G	p.Phe81Cys	missense_variant	Exon 5 of 9		NP_001164194.1	Q5T0J7-5
TEX35	NM_001170724.2 link	c.242T>G	p.Phe81Cys	missense_variant	Exon 5 of 9		NP_001164195.1	Q5T0J7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX35	ENST00000319416.7 link	c.242T>G	p.Phe81Cys	missense_variant	Exon 5 of 9	1	NM_032126.5	ENSP00000323795.2		Q5T0J7-1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000478

GnomAD2 exomes

AF:

0.0000837

AC:

AN:

250920

AF XY:

0.0000737

show subpopulations

Gnomad AFR exome

AF:

0.000926

Gnomad AMR exome

AF:

0.0000869

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:

0.0000294

AC:

AN:

1461472

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

33470

American (AMR)

AF:

0.0000671

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111758

Other (OTH)

AF:

0.0000497

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000276

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41558

American (AMR)

AF:

0.000327

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2114

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:

0.000123

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.242T>G (p.F81C) alteration is located in exon 5 (coding exon 5) of the TEX35 gene. This alteration results from a T to G substitution at nucleotide position 242, causing the phenylalanine (F) at amino acid position 81 to be replaced by a cysteine (C). 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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

T;.;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.39

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.0

L;L;L;.

PhyloP100

3.4

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.2

D;D;D;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.88

MVP

0.53

MPC

0.53

ClinPred

0.38

GERP RS

5.1

Varity_R

0.84

gMVP

0.22

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr1-178516640-T-G

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