9-100310313-T-C

Position:

• chr9-100310313-T-C

Variant summary

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

The ENST00000374902.9(TEX10):​c.2269A>G​(p.Ile757Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEX10 ENST00000374902.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10

Genes affected

TEX10 (HGNC:25988): (testis expressed 10) Located in mitochondrion and nucleoplasm. Part of MLL1 complex. [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=0.17809528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX10	NM_017746.4	c.2269A>G	p.Ile757Val	missense_variant	12/15	ENST00000374902.9	NP_060216.2
TEX10	NM_001161584.2	c.2278A>G	p.Ile760Val	missense_variant	12/15		NP_001155056.1
TEX10	XM_011518798.3	c.1894A>G	p.Ile632Val	missense_variant	10/13		XP_011517100.1
TEX10	XM_047423523.1	c.2269A>G	p.Ile757Val	missense_variant	12/13		XP_047279479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX10	ENST00000374902.9	c.2269A>G	p.Ile757Val	missense_variant	12/15	1	NM_017746.4	ENSP00000364037.4
TEX10	ENST00000535814.5	c.2278A>G	p.Ile760Val	missense_variant	12/15	2		ENSP00000444555.1

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

Sep 27, 2022

The c.2269A>G (p.I757V) alteration is located in exon 12 (coding exon 11) of the TEX10 gene. This alteration results from a A to G substitution at nucleotide position 2269, causing the isoleucine (I) at amino acid position 757 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	0.093
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	.;T
Eigen	Benign	0.077
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.30	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.091	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.60	.;P
Vest4		0.25
MutPred		0.59		.;Gain of ubiquitination at K759 (P = 0.1295);
MVP		0.13
MPC		0.27
ClinPred		0.57	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.070
gMVP		0.26

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: chr9-103072595;