Variant X-124380579-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 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

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:):

STAG2 links:

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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=0.010320634).

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 id is 3042360.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
TENM1	NM_001163278.2 linkuse as main transcript	c.8156A>G	p.Asn2719Ser	missense_variant	35/35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 linkuse as main transcript	c.8153A>G	p.Asn2718Ser	missense_variant	32/32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 linkuse as main transcript	c.8135A>G	p.Asn2712Ser	missense_variant	31/31	NP_055068.2	Q9UKZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
TENM1	ENST00000371130.7 linkuse as main transcript	c.8135A>G	p.Asn2712Ser	missense_variant	31/31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 linkuse as main transcript	c.8102A>G	p.Asn2701Ser	missense_variant	35/35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 linkuse as main transcript	n.454-31243T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

173

AN:

112081

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

34241

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

GnomAD3 exomes

AF:

0.000428

AC:

AN:

179779

Hom.:

AF XY:

0.000263

AC XY:

AN XY:

64571

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 SAS 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

Gnomad4 AFR exome

AF:

0.00668

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000475

Gnomad4 OTH exome

AF:

0.000326

GnomAD4 genome

AF:

0.00154

AC:

173

AN:

112134

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

34304

show subpopulations

Gnomad4 AFR

AF:

0.00544

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.000654

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.00180

ESP6500AA

AF:

0.00678

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000387

AC:

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

0.062

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.042

T;.

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.52

N;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.23

Sift

Benign

0.50

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.013

B;.

Vest4

0.25

MVP

0.63

MPC

0.37

ClinPred

0.026

GERP RS

5.7

Varity_R

0.17

gMVP

0.17

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