13-30952794-G-A

Position:

• chr13-30952794-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152325.3(TEX26):​c.281G>A​(p.Gly94Glu) 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 1,460,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TEX26 NM_152325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0320

Genes affected

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

TEX26 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10850856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX26	NM_152325.3	c.281G>A	p.Gly94Glu	missense_variant	3/7	ENST00000380473.8	NP_689538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX26	ENST00000380473.8	c.281G>A	p.Gly94Glu	missense_variant	3/7	1	NM_152325.3	ENSP00000369840.3
TEX26	ENST00000531960.1	n.138-4079G>A		intron_variant		3		ENSP00000435263.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460416 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726482

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 24, 2022

The c.281G>A (p.G94E) alteration is located in exon 3 (coding exon 3) of the TEX26 gene. This alteration results from a G to A substitution at nucleotide position 281, causing the glycine (G) at amino acid position 94 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.7
DANN	Benign	0.89
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.035
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.034	D
Polyphen		0.48	P
Vest4		0.17
MutPred		0.41		Gain of ubiquitination at K96 (P = 0.0582);
MVP		0.26
MPC		0.0064
ClinPred		0.50	D
GERP RS		1.6
Varity_R		0.23
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-31526931;