chrX-124384398-C-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001163278.2(TENM1):c.6533G>A(p.Arg2178His) variant causes a missense change. The variant allele was found at a frequency of 0.0000314 in 1,209,013 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000034 ( 0 hom. 13 hem. )
Consequence
TENM1
NM_001163278.2 missense
NM_001163278.2 missense
Scores
7
7
3
Clinical Significance
Conservation
PhyloP100: 6.17
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 -4 ACMG points.
BS2
High Hemizygotes in GnomAdExome4 at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TENM1 | NM_001163278.2 | c.6533G>A | p.Arg2178His | missense_variant | Exon 33 of 35 | NP_001156750.1 | ||
TENM1 | NM_001163279.1 | c.6530G>A | p.Arg2177His | missense_variant | Exon 30 of 32 | NP_001156751.1 | ||
TENM1 | NM_014253.3 | c.6512G>A | p.Arg2171His | missense_variant | Exon 29 of 31 | NP_055068.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TENM1 | ENST00000371130.7 | c.6512G>A | p.Arg2171His | missense_variant | Exon 29 of 31 | 1 | ENSP00000360171.3 | |||
TENM1 | ENST00000422452.3 | c.6479G>A | p.Arg2160His | missense_variant | Exon 33 of 35 | 1 | ENSP00000403954.4 | |||
STAG2 | ENST00000469481.1 | n.454-27424C>T | intron_variant | Intron 2 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000901 AC: 1AN: 110958Hom.: 0 Cov.: 23 AF XY: 0.0000301 AC XY: 1AN XY: 33186
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GnomAD3 exomes AF: 0.0000547 AC: 10AN: 182974Hom.: 0 AF XY: 0.0000444 AC XY: 3AN XY: 67598
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GnomAD4 exome AF: 0.0000337 AC: 37AN: 1098055Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 13AN XY: 363445
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GnomAD4 genome AF: 0.00000901 AC: 1AN: 110958Hom.: 0 Cov.: 23 AF XY: 0.0000301 AC XY: 1AN XY: 33186
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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 | May 30, 2024 | The c.6533G>A (p.R2178H) 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 6533, causing the arginine (R) at amino acid position 2178 to be replaced by a histidine (H). 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
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of ubiquitination at K2167 (P = 0.0683);.;
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