X-124384399-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The ENST00000422452.4(TENM1):c.6532C>T(p.Arg2178Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000662 in 1,208,594 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000064 ( 0 hom. 2 hem. )
Consequence
TENM1
ENST00000422452.4 missense
ENST00000422452.4 missense
Scores
11
3
3
Clinical Significance
Conservation
PhyloP100: 5.37
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 -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TENM1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.904
BS2
?
High Hemizygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TENM1 | NM_001163278.2 | c.6532C>T | p.Arg2178Cys | missense_variant | 33/35 | ENST00000422452.4 | |
TENM1 | XM_017029210.3 | c.6631C>T | p.Arg2211Cys | missense_variant | 33/35 | ||
LOC105373331 | XR_938576.1 | n.89-3390G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TENM1 | ENST00000422452.4 | c.6532C>T | p.Arg2178Cys | missense_variant | 33/35 | 1 | NM_001163278.2 | A1 | |
TENM1 | ENST00000371130.7 | c.6511C>T | p.Arg2171Cys | missense_variant | 29/31 | 1 | P4 | ||
STAG2 | ENST00000469481.1 | n.454-27423G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000904 AC: 1AN: 110627Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 32887
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GnomAD3 exomes AF: 0.0000109 AC: 2AN: 182964Hom.: 0 AF XY: 0.0000296 AC XY: 2AN XY: 67590
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GnomAD4 exome AF: 0.00000638 AC: 7AN: 1097967Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 2AN XY: 363357
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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 | Mar 08, 2024 | The c.6532C>T (p.R2178C) alteration is located in exon 30 (coding exon 30) of the TENM1 gene. This alteration results from a C to T substitution at nucleotide position 6532, causing the arginine (R) at amino acid position 2178 to be replaced by a cysteine (C). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of catalytic residue at S2173 (P = 0.0578);.;
MVP
MPC
1.5
ClinPred
D
GERP RS
Varity_R
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