15-56428388-A-G

Position:

• chr15-56428388-A-G

Variant summary

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

The NM_001395496.1(TEX9):​c.1120A>G​(p.Met374Val) 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. 13/21 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)
• Consequence: TEX9 NM_001395496.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

Genes affected

TEX9 (HGNC:29585): (testis expressed 9)

MNS1 (HGNC:29636): (meiosis specific nuclear structural 1) This gene encodes a protein highly similar to the mouse meiosis-specific nuclear structural 1 protein. The mouse protein was shown to be expressed at the pachytene stage during spermatogenesis and may function as a nuclear skeletal protein to regulate nuclear morphology during meiosis. [provided by RefSeq, Oct 2008]

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=0.19904667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX9	NM_001395496.1	c.1120A>G	p.Met374Val	missense_variant	12/12	ENST00000696102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX9	ENST00000696102.1	c.1120A>G	p.Met374Val	missense_variant	12/12		NM_001395496.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Mar 14, 2023

The c.1120A>G (p.M374V) alteration is located in exon 12 (coding exon 12) of the TEX9 gene. This alteration results from a A to G substitution at nucleotide position 1120, causing the methionine (M) at amino acid position 374 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	0.17
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.077	T;.;T
Eigen	Benign	0.042
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.012	D;T;T
Sift4G	Uncertain	0.034	D;D;T
Polyphen		0.92	P;.;.
Vest4		0.71
MutPred		0.31		Loss of disorder (P = 0.0596);.;.;
MVP		0.70
MPC		0.012
ClinPred		0.55	D
GERP RS		3.4
Varity_R		0.29
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: chr15-56720586;