chrX-124384398-C-T

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

Scores

7
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17
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]

Genome browser will be placed here

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
TENM1NM_001163278.2 linkc.6533G>A p.Arg2178His missense_variant Exon 33 of 35 NP_001156750.1 Q9UKZ4-2
TENM1NM_001163279.1 linkc.6530G>A p.Arg2177His missense_variant Exon 30 of 32 NP_001156751.1 Q9UKZ4B7ZMH4
TENM1NM_014253.3 linkc.6512G>A p.Arg2171His missense_variant Exon 29 of 31 NP_055068.2 Q9UKZ4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TENM1ENST00000371130.7 linkc.6512G>A p.Arg2171His missense_variant Exon 29 of 31 1 ENSP00000360171.3 Q9UKZ4-1
TENM1ENST00000422452.3 linkc.6479G>A p.Arg2160His missense_variant Exon 33 of 35 1 ENSP00000403954.4 A0A8Z5AZJ6
STAG2ENST00000469481.1 linkn.454-27424C>T intron_variant Intron 2 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.00000901
AC:
1
AN:
110958
Hom.:
0
Cov.:
23
AF XY:
0.0000301
AC XY:
1
AN XY:
33186
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000189
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000547
AC:
10
AN:
182974
Hom.:
0
AF XY:
0.0000444
AC XY:
3
AN XY:
67598
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000157
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000490
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000337
AC:
37
AN:
1098055
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
13
AN XY:
363445
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.0000852
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000924
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000285
Gnomad4 OTH exome
AF:
0.0000868
GnomAD4 genome
AF:
0.00000901
AC:
1
AN:
110958
Hom.:
0
Cov.:
23
AF XY:
0.0000301
AC XY:
1
AN XY:
33186
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000189
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsMay 30, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.44
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.26
T;.
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Pathogenic
0.31
D
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Uncertain
0.75
D
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-4.2
D;D
REVEL
Pathogenic
0.83
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.41
MutPred
0.52
Loss of ubiquitination at K2167 (P = 0.0683);.;
MVP
0.91
MPC
1.5
ClinPred
0.63
D
GERP RS
5.5
Varity_R
0.76
gMVP
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs762426434; hg19: chrX-123518248; COSMIC: COSV64428703; API