19-43418281-C-G

Position:

• chr19-43418281-C-G

Variant summary

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

The NM_001130011.3(TEX101):​c.634C>G​(p.Gln212Glu) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEX101 NM_001130011.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.649

Genes affected

TEX101 (HGNC:30722): (testis expressed 101) Predicted to be involved in binding activity of sperm to zona pellucida; flagellated sperm motility; and regulation of flagellated sperm motility. Predicted to be located in acrosomal vesicle; extracellular region; and plasma membrane. Predicted to be active in plasma membrane raft. Predicted to be anchored component of plasma membrane. [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=0.12108785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX101	NM_001130011.3	c.634C>G	p.Gln212Glu	missense_variant	6/6	ENST00000598265.2	NP_001123483.1
TEX101	NM_031451.5	c.688C>G	p.Gln230Glu	missense_variant	9/9		NP_113639.4
TEX101	XM_005259303.4	c.730C>G	p.Gln244Glu	missense_variant	6/6		XP_005259360.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX101	ENST00000598265.2	c.634C>G	p.Gln212Glu	missense_variant	6/6	1	NM_001130011.3	ENSP00000472769	P2
TEX101	ENST00000602198.5	c.688C>G	p.Gln230Glu	missense_variant	8/8	5		ENSP00000472308	A2
TEX101	ENST00000601707.1	n.738C>G		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jul 20, 2022

The c.688C>G (p.Q230E) alteration is located in exon 9 (coding exon 6) of the TEX101 gene. This alteration results from a C to G substitution at nucleotide position 688, causing the glutamine (Q) at amino acid position 230 to be replaced by a glutamic acid (E). 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	0.079
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.39
DEOGEN2	Benign	0.0048	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	.;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.17	T;T
Polyphen		0.24	B;B
Vest4		0.18
MutPred		0.45		.;Gain of disorder (P = 0.1299);
MVP		0.12
MPC		0.25
ClinPred		0.98	D
GERP RS		0.82
Varity_R		0.042
gMVP		0.33

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: chr19-43922433;