rs948852498

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001163278.2(TENM1):c.7444A>G(p.Ile2482Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,193,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

TENM1
NM_001163278.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

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]

TENM1 links:

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]

STAG2 links:

LOC105373331 (HGNC:):

LOC105373331 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15770888).

BP6

Variant X-124381291-T-C is Benign according to our data. Variant chrX-124381291-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3771907.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
TENM1	NM_001163278.2 link	c.7444A>G	p.Ile2482Val	missense_variant	Exon 35 of 35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 link	c.7441A>G	p.Ile2481Val	missense_variant	Exon 32 of 32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 link	c.7423A>G	p.Ile2475Val	missense_variant	Exon 31 of 31	NP_055068.2	Q9UKZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
TENM1	ENST00000371130.7 link	c.7423A>G	p.Ile2475Val	missense_variant	Exon 31 of 31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 link	c.7390A>G	p.Ile2464Val	missense_variant	Exon 35 of 35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 link	n.454-30531T>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111822

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33996

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1081393

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

354851

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000358

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111822

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33996

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:

0.0000188

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TENM1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.024

T;.

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.34

N;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.24

Sift

Benign

0.23

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0

B;.

Vest4

0.056

MutPred

0.37

Loss of catalytic residue at I2475 (P = 0.0563);.;

MVP

0.49

MPC

0.39

ClinPred

0.077

GERP RS

4.7

Varity_R

0.11

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over