chrX-124380579-T-C

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.8156A>G(p.Asn2719Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000312 in 1,208,812 control chromosomes in the GnomAD database, including 2 homozygotes. There are 89 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., 41 hem., cov: 23)

Exomes 𝑓: 0.00019 ( 1 hom. 48 hem. )

Consequence

TENM1
NM_001163278.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.10

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:

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=0.010320634).

BP6

Variant X-124380579-T-C is Benign according to our data. Variant chrX-124380579-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3042360.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 173 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.8156A>G	p.Asn2719Ser	missense	Exon 35 of 35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1		c.8153A>G	p.Asn2718Ser	missense	Exon 32 of 32	NP_001156751.1	B7ZMH4
TENM1	NM_014253.3		c.8135A>G	p.Asn2712Ser	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.8156A>G	p.Asn2719Ser	missense	Exon 35 of 35	ENSP00000403954.4	Q9UKZ4-2
TENM1	ENST00000371130.7	TSL:1	c.8135A>G	p.Asn2712Ser	missense	Exon 31 of 31	ENSP00000360171.3	Q9UKZ4-1
STAG2	ENST00000469481.1	TSL:3	n.454-31243T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

173

AN:

112081

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00545

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

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:

0.0000375

Gnomad OTH

AF:

0.000662

GnomAD2 exomes

AF:

0.000428

AC:

AN:

179779

AF XY:

0.000263

show subpopulations

Gnomad AFR exome

AF:

0.00533

Gnomad AMR exome

AF:

0.000185

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.000186

AC:

204

AN:

1096678

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

362224

show subpopulations

African (AFR)

AF:

0.00668

AC:

176

AN:

26365

American (AMR)

AF:

0.000257

AC:

AN:

35075

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19276

East Asian (EAS)

AF:

0.00

AC:

AN:

30193

South Asian (SAS)

AF:

0.00

AC:

AN:

53850

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4115

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

841296

Other (OTH)

AF:

0.000326

AC:

AN:

46028

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

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:

0.00154

AC:

173

AN:

112134

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

34304

show subpopulations

African (AFR)

AF:

0.00544

AC:

168

AN:

30907

American (AMR)

AF:

0.000189

AC:

AN:

10596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3557

South Asian (SAS)

AF:

0.00

AC:

AN:

2660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000375

AC:

AN:

53264

Other (OTH)

AF:

0.000654

AC:

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000698

Hom.:

Bravo

AF:

0.00180

ESP6500AA

AF:

0.00678

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000387

AC:

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

0.062

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.042

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.52

PhyloP100

4.1

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.1

REVEL

Benign

0.23

Sift

Benign

0.50

Sift4G

Benign

0.42

Polyphen

0.013

Vest4

0.25

MVP

0.63

MPC

0.37

ClinPred

0.026

GERP RS

5.7

Varity_R

0.17

gMVP

0.17

Mutation Taster

=96/4

polymorphism

(source)

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

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