chr13-30957012-T-C

Position:

• chr13-30957012-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152325.3(TEX26):​c.452T>C​(p.Phe151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 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: 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: 0.432

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX26	NM_152325.3	c.452T>C	p.Phe151Ser	missense_variant	4/7	ENST00000380473.8	NP_689538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX26	ENST00000380473.8	c.452T>C	p.Phe151Ser	missense_variant	4/7	1	NM_152325.3	ENSP00000369840	P1
TEX26	ENST00000530916.1	n.55T>C		non_coding_transcript_exon_variant	1/2	3
TEX26	ENST00000531960.1	c.*91T>C		3_prime_UTR_variant, NMD_transcript_variant	3/6	3		ENSP00000435263

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

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 16, 2023

The c.452T>C (p.F151S) alteration is located in exon 4 (coding exon 4) of the TEX26 gene. This alteration results from a T to C substitution at nucleotide position 452, causing the phenylalanine (F) at amino acid position 151 to be replaced by a serine (S). 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	0.71
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.70
MVP		0.51
MPC		0.021
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.70
gMVP		0.41

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

Other links and lift over

dbSNP: rs1954162888; hg19: chr13-31531149;