14-105399360-C-G

Variant names:

• chr14-105399360-C-G
• rs1311253989
• NM_001195082.2:c.20C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195082.2(TEX22):​c.20C>G​(p.Ser7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,380,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TEX22 NM_001195082.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.572

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039862484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX22	NM_001195082.2	c.20C>G	p.Ser7Cys	missense_variant	Exon 2 of 4	ENST00000451127.3	NP_001182011.1
TEX22	XM_006720234.4	c.20C>G	p.Ser7Cys	missense_variant	Exon 2 of 4		XP_006720297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX22	ENST00000451127.3	c.20C>G	p.Ser7Cys	missense_variant	Exon 2 of 4	2	NM_001195082.2	ENSP00000397002.2
TEX22	ENST00000548638.5	n.20C>G		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000449736.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1380748 Hom.: 0 Cov.: 34 AF XY: 0.00000147 AC XY: 1 AN XY: 681324

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: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20C>G (p.S7C) alteration is located in exon 2 (coding exon 1) of the TEX22 gene. This alteration results from a C to G substitution at nucleotide position 20, causing the serine (S) at amino acid position 7 to be replaced by a cysteine (C). 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	0.083
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.6
DANN	Benign	0.65
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.027
Sift	Benign	0.15	T
Sift4G	Benign	0.092	T
Polyphen		0.0020	B
Vest4		0.068
MutPred		0.21		Loss of phosphorylation at S7 (P = 0.0015);
MVP		0.030
ClinPred		0.047	T
GERP RS		-2.6
Varity_R		0.049
gMVP		0.013

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: rs1311253989; hg19: chr14-105865697;