ENST00000371130.7:c.6512G>A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000371130.7(TENM1):c.6512G>A(p.Arg2171His) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2171C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000034 ( 0 hom. 13 hem. )

Consequence

TENM1
ENST00000371130.7 missense

Scores

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]

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
TENM1	NM_001163278.2 link	c.6533G>A	p.Arg2178His	missense_variant	Exon 33 of 35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 link	c.6530G>A	p.Arg2177His	missense_variant	Exon 30 of 32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 link	c.6512G>A	p.Arg2171His	missense_variant	Exon 29 of 31	NP_055068.2	Q9UKZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
TENM1	ENST00000371130.7 link	c.6512G>A	p.Arg2171His	missense_variant	Exon 29 of 31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 link	c.6479G>A	p.Arg2160His	missense_variant	Exon 33 of 35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 link	n.454-27424C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00000901

AC:

AN:

110958

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

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:

AN:

182974

Hom.:

AF XY:

0.0000444

AC XY:

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:

AN:

1098055

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

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:

AN:

110958

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

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:

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 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.44

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

T;.

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Uncertain

0.75

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Pathogenic

0.82

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

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.

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