X-124381186-C-T

Position:

chrX-124381186-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The ENST00000422452.4(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. 14/20 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
ENST00000422452.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.09

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:

LOC105373331 (HGNC:):

LOC105373331 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TENM1. . Gene score misZ 3.4329 (greater than the threshold 3.09). GenCC has associacion of gene with anosmia, cerebral palsy, isolated congenital anosmia.

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 id is 3052802.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TENM1	NM_001163278.2 linkuse as main transcript	c.7549G>A	p.Gly2517Arg	missense_variant	35/35	ENST00000422452.4	NP_001156750.1
TENM1	XM_017029210.3 linkuse as main transcript	c.7648G>A	p.Gly2550Arg	missense_variant	35/35		XP_016884699.1
LOC105373331	XR_938576.1 linkuse as main transcript	n.88+192C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM1	ENST00000422452.4 linkuse as main transcript	c.7549G>A	p.Gly2517Arg	missense_variant	35/35	1	NM_001163278.2	ENSP00000403954	A1
TENM1	ENST00000371130.7 linkuse as main transcript	c.7528G>A	p.Gly2510Arg	missense_variant	31/31	1		ENSP00000360171	P4	Q9UKZ4-1
STAG2	ENST00000469481.1 linkuse as main transcript	n.454-30636C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000187

AC:

AN:

112062

Hom.:

Cov.:

AF XY:

0.000292

AC XY:

AN XY:

34226

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

GnomAD3 exomes

AF:

0.000639

AC:

115

AN:

180062

Hom.:

AF XY:

0.00113

AC XY:

AN XY:

65696

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 SAS exome

AF:

0.00540

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00598

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000962

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000196

AC:

AN:

112116

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

AN XY:

34290

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.0000943

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00558

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.000652

Alfa

AF:

0.000213

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TENM1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.025

T;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.41

N;.

MutationTaster

Benign

0.95

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.18

Sift

Benign

0.11

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.12

B;.

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

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

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