chr13-30952739-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152325.3(TEX26):​c.226T>A​(p.Tyr76Asn) 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 1,612,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TEX26
NM_152325.3 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44
Variant links:
Genes affected
TEX26 (HGNC:28622): (testis expressed 26) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TEX26NM_152325.3 linkuse as main transcriptc.226T>A p.Tyr76Asn missense_variant 3/7 ENST00000380473.8 NP_689538.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TEX26ENST00000380473.8 linkuse as main transcriptc.226T>A p.Tyr76Asn missense_variant 3/71 NM_152325.3 ENSP00000369840 P1
TEX26ENST00000531960.1 linkuse as main transcriptc.138-4134T>A intron_variant, NMD_transcript_variant 3 ENSP00000435263

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00000398
AC:
1
AN:
251018
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135666
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1460634
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
726668
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:
0.0000189
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
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
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 09, 2021The c.226T>A (p.Y76N) alteration is located in exon 3 (coding exon 3) of the TEX26 gene. This alteration results from a T to A substitution at nucleotide position 226, causing the tyrosine (Y) at amino acid position 76 to be replaced by an asparagine (N). 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
0.67
BayesDel_addAF
Uncertain
0.078
D
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.081
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.023
T
MetaRNN
Pathogenic
0.75
D
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
0.65
D
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-6.1
D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.79
MutPred
0.47
Loss of sheet (P = 0.0104);
MVP
0.53
MPC
0.023
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.71
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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.

Other links and lift over

dbSNP: rs767032519; hg19: chr13-31526876; API