X-124381186-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001163278.2(TENM1):c.7549G>A(p.Gly2517Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,207,961 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 249 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 11 hem., cov: 23)

Exomes 𝑓: 0.00040 ( 0 hom. 238 hem. )

Consequence

TENM1
NM_001163278.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.09

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Mullegama-Klein-Martinez syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
Xq25 microduplication syndrome
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

STAG2 links:

LOC105373331 (HGNC:):

LOC105373331 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006038189).

BP6

Variant X-124381186-C-T is Benign according to our data. Variant chrX-124381186-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3052802.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 22 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163278.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENM1	NM_001163278.2	MANE Select	c.7549G>A	p.Gly2517Arg	missense	Exon 35 of 35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1		c.7546G>A	p.Gly2516Arg	missense	Exon 32 of 32	NP_001156751.1	B7ZMH4
TENM1	NM_014253.3		c.7528G>A	p.Gly2510Arg	missense	Exon 31 of 31	NP_055068.2	Q9UKZ4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENM1	ENST00000422452.4	TSL:1 MANE Select	c.7549G>A	p.Gly2517Arg	missense	Exon 35 of 35	ENSP00000403954.4	Q9UKZ4-2
TENM1	ENST00000371130.7	TSL:1	c.7528G>A	p.Gly2510Arg	missense	Exon 31 of 31	ENSP00000360171.3	Q9UKZ4-1
STAG2	ENST00000469481.1	TSL:3	n.454-30636C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000187

AC:

AN:

112062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000944

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.000661

GnomAD2 exomes

AF:

0.000639

AC:

115

AN:

180062

AF XY:

0.00113

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000986

Gnomad OTH exome

AF:

0.000667

GnomAD4 exome

AF:

0.000401

AC:

439

AN:

1095845

Hom.:

Cov.:

AF XY:

0.000657

AC XY:

238

AN XY:

362117

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26393

American (AMR)

AF:

0.0000284

AC:

AN:

35200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19381

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.00598

AC:

324

AN:

54141

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38310

Middle Eastern (MID)

AF:

0.00532

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000962

AC:

AN:

842002

Other (OTH)

AF:

0.000239

AC:

AN:

46080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000196

AC:

AN:

112116

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

AN XY:

34290

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30874

American (AMR)

AF:

0.0000943

AC:

AN:

10604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3546

South Asian (SAS)

AF:

0.00558

AC:

AN:

2687

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

53212

Other (OTH)

AF:

0.000652

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00101

AC:

122

EpiCase

AF:

0.000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

TENM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.025

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.41

PhyloP100

3.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.96

REVEL

Benign

0.18

Sift

Benign

0.11

Sift4G

Benign

0.42

Polyphen

0.12

Vest4

0.098

MutPred

0.33

Gain of solvent accessibility (P = 0.019)

MVP

0.44

MPC

0.58

ClinPred

0.025

GERP RS

5.8

Varity_R

0.26

gMVP

0.72

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over