11-112171809-A-G

Position:

• chr11-112171809-A-G

Variant summary

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

The NM_031275.4(TEX12):​c.265A>G​(p.Ile89Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TEX12 NM_031275.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.126

Genes affected

TEX12 (HGNC:11734): (testis expressed 12) This gene is similar to a mouse gene that is expressed in the testis. [provided by RefSeq, Jul 2008]

ENSG00000255292 (HGNC:):

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=0.042803466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX12	NM_031275.4	c.265A>G	p.Ile89Val	missense_variant	5/5	ENST00000280358.5	NP_112565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX12	ENST00000280358.5	c.265A>G	p.Ile89Val	missense_variant	5/5	1	NM_031275.4	ENSP00000280358.4
ENSG00000255292	ENST00000532699.1	n.*55+1135A>G		intron_variant		3		ENSP00000456434.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437396 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 714856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000506

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

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

Oct 25, 2024

The c.265A>G (p.I89V) alteration is located in exon 5 (coding exon 4) of the TEX12 gene. This alteration results from a A to G substitution at nucleotide position 265, causing the isoleucine (I) at amino acid position 89 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.056
Sift	Benign	0.061	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0	B;B
Vest4		0.27
MutPred		0.22		Gain of phosphorylation at Y85 (P = 0.086);Gain of phosphorylation at Y85 (P = 0.086);
MVP		0.048
MPC		0.088
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.062
gMVP		0.093

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

LitVar

Other links and lift over

dbSNP: rs1866794157; hg19: chr11-112042532;