13-30939726-A-G

Position:

• chr13-30939726-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152325.3(TEX26):​c.94A>G​(p.Thr32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TEX26 NM_152325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX26	NM_152325.3	c.94A>G	p.Thr32Ala	missense_variant	2/7	ENST00000380473.8	NP_689538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX26	ENST00000380473.8	c.94A>G	p.Thr32Ala	missense_variant	2/7	1	NM_152325.3	ENSP00000369840	P1
TEX26	ENST00000531960.1	c.85A>G	p.Thr29Ala	missense_variant, NMD_transcript_variant	2/6	3		ENSP00000435263

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.94A>G (p.T32A) alteration is located in exon 2 (coding exon 2) of the TEX26 gene. This alteration results from a A to G substitution at nucleotide position 94, causing the threonine (T) at amino acid position 32 to be replaced by an alanine (A). 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	0.24
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.74
MutPred		0.32		Gain of helix (P = 0.027);
MVP		0.45
MPC		0.022
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.56
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

Other links and lift over

dbSNP: rs374045694; hg19: chr13-31513863;