ENST00000371130.7:c.8087A>G

Variant names:

• chrX-124380627-T-C
• ENST00000371130.7:c.8087A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000371130.7(TENM1):​c.8087A>G​(p.Tyr2696Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TENM1 ENST00000371130.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

Genes affected

TENM1 (HGNC:8117): (teneurin transmembrane protein 1) The protein encoded by this gene belongs to the tenascin family and teneurin subfamily. It is expressed in the neurons and may function as a cellular signal transducer. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM1	NM_001163278.2	c.8108A>G	p.Tyr2703Cys	missense_variant	Exon 35 of 35		NP_001156750.1
TENM1	NM_001163279.1	c.8105A>G	p.Tyr2702Cys	missense_variant	Exon 32 of 32		NP_001156751.1
TENM1	NM_014253.3	c.8087A>G	p.Tyr2696Cys	missense_variant	Exon 31 of 31		NP_055068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000371130.7	c.8087A>G	p.Tyr2696Cys	missense_variant	Exon 31 of 31	1		ENSP00000360171.3
TENM1	ENST00000422452.3	c.8054A>G	p.Tyr2685Cys	missense_variant	Exon 35 of 35	1		ENSP00000403954.4
STAG2	ENST00000469481.1	n.454-31195T>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8108A>G (p.Y2703C) alteration is located in exon 32 (coding exon 32) of the TENM1 gene. This alteration results from a A to G substitution at nucleotide position 8108, causing the tyrosine (Y) at amino acid position 2703 to be replaced by a cysteine (C). 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	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.69	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.015	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.42		Loss of phosphorylation at Y2696 (P = 0.0457);.;
MVP		0.89
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.64

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: chrX-123514477;