9-100327862-T-C

Position:

• chr9-100327862-T-C

Variant summary

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

The NM_017746.4(TEX10):​c.1726A>G​(p.Ile576Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: TEX10 NM_017746.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18

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=0.097743124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX10	NM_017746.4	c.1726A>G	p.Ile576Val	missense_variant	8/15	ENST00000374902.9	NP_060216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX10	ENST00000374902.9	c.1726A>G	p.Ile576Val	missense_variant	8/15	1	NM_017746.4	ENSP00000364037	P1
TEX10	ENST00000535814.5	c.1735A>G	p.Ile579Val	missense_variant	8/15	2		ENSP00000444555

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456620 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724528

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: 9.02e-7

Gnomad4 OTH exome AF: 0.0000166

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

May 01, 2024

The c.1726A>G (p.I576V) alteration is located in exon 8 (coding exon 7) of the TEX10 gene. This alteration results from a A to G substitution at nucleotide position 1726, causing the isoleucine (I) at amino acid position 576 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	0.095
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;L
MutationTaster	Benign	0.73	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.19	N;N
REVEL	Benign	0.039
Sift	Benign	0.61	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.013	.;B
Vest4		0.33
MutPred		0.27		.;Loss of catalytic residue at A580 (P = 0.138);
MVP		0.12
MPC		0.27
ClinPred		0.31	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.031
gMVP		0.094

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: rs368352983; hg19: chr9-103090144;