14-105411720-C-T

Position:

• chr14-105411720-C-T

Variant summary

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

The NM_001195082.2(TEX22):​c.340C>T​(p.Pro114Ser) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEX22 NM_001195082.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.989

Genes affected

TEX22 (HGNC:40026): (testis expressed 22) Predicted to be located 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=0.07643169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX22	NM_001195082.2	c.340C>T	p.Pro114Ser	missense_variant	4/4	ENST00000451127.3	NP_001182011.1
TEX22	XM_006720234.4	c.340C>T	p.Pro114Ser	missense_variant	4/4		XP_006720297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX22	ENST00000451127.3	c.340C>T	p.Pro114Ser	missense_variant	4/4	2	NM_001195082.2	ENSP00000397002.2
TEX22	ENST00000548638.5	n.150+12230C>T		intron_variant		5		ENSP00000449736.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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, 2024

The c.340C>T (p.P114S) alteration is located in exon 4 (coding exon 3) of the TEX22 gene. This alteration results from a C to T substitution at nucleotide position 340, causing the proline (P) at amino acid position 114 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	Benign	0.21
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.028
Sift	Benign	0.42	T
Sift4G	Benign	0.62	T
Polyphen		0.27	B
Vest4		0.14
MutPred		0.30		Gain of sheet (P = 0.0221);
MVP		0.030
ClinPred		0.21	T
GERP RS		-0.32
Varity_R		0.045
gMVP		0.022

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-105878057;