13-30969005-C-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.767C>A(p.Ser256Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TEX26 NM_152325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.169864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX26	NM_152325.3	c.767C>A	p.Ser256Tyr	missense_variant	6/7	ENST00000380473.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX26	ENST00000380473.8	c.767C>A	p.Ser256Tyr	missense_variant	6/7	1	NM_152325.3	P1
TEX26	ENST00000531960.1	c.*406C>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	3
TEX26	ENST00000530916.1	n.73-5841C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Feb 06, 2024

The c.767C>A (p.S256Y) alteration is located in exon 6 (coding exon 6) of the TEX26 gene. This alteration results from a C to A substitution at nucleotide position 767, causing the serine (S) at amino acid position 256 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	18
Dann	Benign	0.95
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.95	P
Vest4		0.32
MutPred		0.33		Loss of disorder (P = 0.032);
MVP		0.28
MPC		0.019
ClinPred		0.41	T
GERP RS		4.0
Varity_R		0.082
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-31543142;