Genetic Variant TEX36:p.Phe154Leu (chr10-125656001-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001128202.3(TEX36):c.460T>C(p.Phe154Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,551,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TEX36
NM_001128202.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.817

Variant links:

Genes affected

TEX36 (HGNC:31653): (testis expressed 36)

TEX36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08082825).

BP6

Variant 10-125656001-A-G is Benign according to our data. Variant chr10-125656001-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3806229.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX36	NM_001128202.3 link	c.460T>C	p.Phe154Leu	missense_variant	Exon 4 of 4	ENST00000368821.4	NP_001121674.1	Q5VZQ5
TEX36	NM_001318133.2 link	c.264+5020T>C		intron_variant	Intron 3 of 3		NP_001305062.1	Q5VZQ5A0PJZ8E9PJL2
TEX36	XM_005269817.5 link	c.264+5020T>C		intron_variant	Intron 3 of 3		XP_005269874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEX36	ENST00000368821.4 link	c.460T>C	p.Phe154Leu	missense_variant	Exon 4 of 4	1	NM_001128202.3	ENSP00000357811.3	Q5VZQ5
TEX36	ENST00000532135.5 link	c.264+5020T>C		intron_variant	Intron 3 of 3	1		ENSP00000431764.1	E9PJL2
TEX36	ENST00000526819.5 link	c.264+5020T>C		intron_variant	Intron 3 of 3	5		ENSP00000434299.1	E9PR91

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000317

AC:

AN:

157804

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

83306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000814

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000118

AC:

165

AN:

1399610

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

690272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000152

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 18, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.6

DANN

Benign

0.70

DEOGEN2

Benign

0.0093

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.32

M_CAP

Benign

0.0040

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.1

REVEL

Benign

0.047

Sift

Benign

0.44

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.083

MutPred

0.29

Gain of MoRF binding (P = 0.1215);

MVP

0.040

ClinPred

0.064

GERP RS

2.6

Varity_R

0.079

gMVP

0.13

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