X-124384668-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The ENST00000422452.4(TENM1):c.6263G>A(p.Ser2088Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,208,471 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000091 ( 0 hom. 3 hem. )
Consequence
TENM1
ENST00000422452.4 missense
ENST00000422452.4 missense
Scores
3
7
7
Clinical Significance
Conservation
PhyloP100: 6.08
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 Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, TENM1
BS2
High Hemizygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TENM1 | NM_001163278.2 | c.6263G>A | p.Ser2088Asn | missense_variant | 33/35 | ENST00000422452.4 | |
TENM1 | XM_017029210.3 | c.6362G>A | p.Ser2121Asn | missense_variant | 33/35 | ||
LOC105373331 | XR_938576.1 | n.89-3121C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TENM1 | ENST00000422452.4 | c.6263G>A | p.Ser2088Asn | missense_variant | 33/35 | 1 | NM_001163278.2 | A1 | |
TENM1 | ENST00000371130.7 | c.6242G>A | p.Ser2081Asn | missense_variant | 29/31 | 1 | P4 | ||
STAG2 | ENST00000469481.1 | n.454-27154C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000268 AC: 3AN: 111781Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33945
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GnomAD3 exomes AF: 0.0000109 AC: 2AN: 182821Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67423
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GnomAD4 exome AF: 0.00000912 AC: 10AN: 1096690Hom.: 0 Cov.: 31 AF XY: 0.00000828 AC XY: 3AN XY: 362112
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GnomAD4 genome AF: 0.0000268 AC: 3AN: 111781Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33945
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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 | Dec 08, 2023 | The c.6263G>A (p.S2088N) alteration is located in exon 30 (coding exon 30) of the TENM1 gene. This alteration results from a G to A substitution at nucleotide position 6263, causing the serine (S) at amino acid position 2088 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
0.57
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at