X-124384555-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The ENST00000422452.4(TENM1):c.6376A>G(p.Ile2126Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,874 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )
Consequence
TENM1
ENST00000422452.4 missense
ENST00000422452.4 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 4.19
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, TENM1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24159628).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TENM1 | NM_001163278.2 | c.6376A>G | p.Ile2126Val | missense_variant | 33/35 | ENST00000422452.4 | |
TENM1 | XM_017029210.3 | c.6475A>G | p.Ile2159Val | missense_variant | 33/35 | ||
LOC105373331 | XR_938576.1 | n.89-3234T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TENM1 | ENST00000422452.4 | c.6376A>G | p.Ile2126Val | missense_variant | 33/35 | 1 | NM_001163278.2 | A1 | |
TENM1 | ENST00000371130.7 | c.6355A>G | p.Ile2119Val | missense_variant | 29/31 | 1 | P4 | ||
STAG2 | ENST00000469481.1 | n.454-27267T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097874Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 363254
GnomAD4 exome
AF:
AC:
2
AN:
1097874
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
363254
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
Alfa
AF:
Hom.:
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2023 | The c.6376A>G (p.I2126V) alteration is located in exon 30 (coding exon 30) of the TENM1 gene. This alteration results from a A to G substitution at nucleotide position 6376, causing the isoleucine (I) at amino acid position 2126 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Gain of sheet (P = 0.0016);.;
MVP
MPC
0.43
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at