chrX-124382707-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001163278.2(TENM1):c.7403G>A(p.Arg2468Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000415 in 1,204,412 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2468L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000037 ( 0 hom. 3 hem. )

Consequence

TENM1
NM_001163278.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.94

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.069639325).

BP6

Variant X-124382707-C-T is Benign according to our data. Variant chrX-124382707-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3454784.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 3 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.7403G>A	p.Arg2468Gln	missense	Exon 34 of 35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1		c.7400G>A	p.Arg2467Gln	missense	Exon 31 of 32	NP_001156751.1	B7ZMH4
TENM1	NM_014253.3		c.7382G>A	p.Arg2461Gln	missense	Exon 30 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.7403G>A	p.Arg2468Gln	missense	Exon 34 of 35	ENSP00000403954.4	Q9UKZ4-2
TENM1	ENST00000371130.7	TSL:1	c.7382G>A	p.Arg2461Gln	missense	Exon 30 of 31	ENSP00000360171.3	Q9UKZ4-1
STAG2	ENST00000469481.1	TSL:3	n.454-29115C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000903

AC:

AN:

110701

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000328

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000169

AC:

AN:

177199

AF XY:

0.0000321

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000152

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1093711

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

359749

show subpopulations

African (AFR)

AF:

0.0000382

AC:

AN:

26191

American (AMR)

AF:

0.00

AC:

AN:

34681

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19299

East Asian (EAS)

AF:

0.0000335

AC:

AN:

29837

South Asian (SAS)

AF:

0.0000374

AC:

AN:

53407

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40463

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839801

Other (OTH)

AF:

0.00

AC:

AN:

45914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000903

AC:

AN:

110701

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32971

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000328

AC:

AN:

30514

American (AMR)

AF:

0.00

AC:

AN:

10334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2641

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.00

AC:

AN:

2650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5715

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52892

Other (OTH)

AF:

0.00

AC:

AN:

1475

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.030

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.82

M_CAP

Benign

0.039

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.55

PhyloP100

3.9

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.080

REVEL

Benign

0.19

Sift

Benign

0.99

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.077

MutPred

0.38

Loss of helix (P = 0.0626)

MVP

0.29

MPC

0.54

ClinPred

0.056

GERP RS

4.3

Varity_R

0.058

gMVP

0.19

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over