ENST00000371130.7:c.8087A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_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

Scores

8
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92
Variant links:
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]

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ACMG classification

Classification made for transcript

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
TENM1NM_001163278.2 linkc.8108A>G p.Tyr2703Cys missense_variant Exon 35 of 35 NP_001156750.1 Q9UKZ4-2
TENM1NM_001163279.1 linkc.8105A>G p.Tyr2702Cys missense_variant Exon 32 of 32 NP_001156751.1 Q9UKZ4B7ZMH4
TENM1NM_014253.3 linkc.8087A>G p.Tyr2696Cys missense_variant Exon 31 of 31 NP_055068.2 Q9UKZ4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TENM1ENST00000371130.7 linkc.8087A>G p.Tyr2696Cys missense_variant Exon 31 of 31 1 ENSP00000360171.3 Q9UKZ4-1
TENM1ENST00000422452.3 linkc.8054A>G p.Tyr2685Cys missense_variant Exon 35 of 35 1 ENSP00000403954.4 A0A8Z5AZJ6
STAG2ENST00000469481.1 linkn.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
LINK: link

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; API