14-105399447-G-A

Variant names:

• chr14-105399447-G-A
• NM_001195082.2:c.107G>A

Variant summary

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

The NM_001195082.2(TEX22):​c.107G>A​(p.Ser36Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TEX22 NM_001195082.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0900

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=0.03918913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX22	NM_001195082.2	c.107G>A	p.Ser36Asn	missense_variant	Exon 2 of 4	ENST00000451127.3	NP_001182011.1
TEX22	XM_006720234.4	c.107G>A	p.Ser36Asn	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.107G>A	p.Ser36Asn	missense_variant	Exon 2 of 4	2	NM_001195082.2	ENSP00000397002.2
TEX22	ENST00000548638.5	n.107G>A		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000449736.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383424 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 682638

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.107G>A (p.S36N) alteration is located in exon 2 (coding exon 1) of the TEX22 gene. This alteration results from a G to A substitution at nucleotide position 107, causing the serine (S) at amino acid position 36 to be replaced by an asparagine (N). 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	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.5
DANN	Benign	0.72
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.038
Sift	Benign	0.60	T
Sift4G	Benign	0.96	T
Polyphen		0.048	B
Vest4		0.065
MutPred		0.11		Gain of loop (P = 0.1069);
MVP		0.030
ClinPred		0.040	T
GERP RS		1.6
Varity_R		0.037
gMVP		0.0099

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: chr14-105865784; COSMIC: COSV57653137; COSMIC: COSV57653137;