Genetic Variant TEX35:p.Glu58Lys (chr1-178515871-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032126.5(TEX35):c.172G>A(p.Glu58Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E58Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TEX35
NM_032126.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.08

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37233627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5 link	c.172G>A	p.Glu58Lys	missense_variant	Exon 4 of 9	ENST00000319416.7	NP_115502.2	Q5T0J7-1
TEX35	NM_001170722.2 link	c.196G>A	p.Glu66Lys	missense_variant	Exon 4 of 9		NP_001164193.1	Q5T0J7-2
TEX35	NM_001170723.2 link	c.172G>A	p.Glu58Lys	missense_variant	Exon 4 of 9		NP_001164194.1	Q5T0J7-5
TEX35	NM_001170724.2 link	c.172G>A	p.Glu58Lys	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>A	p.Glu58Lys	missense_variant	Exon 4 of 9	1	NM_032126.5	ENSP00000323795.2		Q5T0J7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459908

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726136

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

60324

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;.;.;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.37

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

L;L;L;.

PhyloP100

2.1

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.40

MutPred

0.37

Gain of MoRF binding (P = 0.0039);Gain of MoRF binding (P = 0.0039);Gain of MoRF binding (P = 0.0039);.;

MVP

0.46

MPC

0.45

ClinPred

0.97

GERP RS

5.4

Varity_R

0.39

gMVP

0.13

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over