X-124384361-T-A

Position:

chrX-124384361-T-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The ENST00000422452.4(TENM1):c.6570A>T(p.Leu2190Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 1,209,457 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 10 hem., cov: 22)

Exomes 𝑓: 0.000027 ( 0 hom. 6 hem. )

Consequence

TENM1
ENST00000422452.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.397

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 -7 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=0.042735815).

BS2

High Hemizygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TENM1	NM_001163278.2 linkuse as main transcript	c.6570A>T	p.Leu2190Phe	missense_variant	33/35	ENST00000422452.4	NP_001156750.1
TENM1	XM_017029210.3 linkuse as main transcript	c.6669A>T	p.Leu2223Phe	missense_variant	33/35		XP_016884699.1
LOC105373331	XR_938576.1 linkuse as main transcript	n.88+3367T>A		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.6570A>T	p.Leu2190Phe	missense_variant	33/35	1	NM_001163278.2	ENSP00000403954	A1
TENM1	ENST00000371130.7 linkuse as main transcript	c.6549A>T	p.Leu2183Phe	missense_variant	29/31	1		ENSP00000360171	P4	Q9UKZ4-1
STAG2	ENST00000469481.1 linkuse as main transcript	n.454-27461T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000234

AC:

AN:

111331

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

AN XY:

33503

show subpopulations

Gnomad AFR

AF:

0.000752

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

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:

0.000671

GnomAD3 exomes

AF:

0.0000929

AC:

AN:

182912

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67516

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.000110

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000273

AC:

AN:

1098073

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363461

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.0000568

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000251

AC:

AN:

111384

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

AN XY:

33566

show subpopulations

Gnomad4 AFR

AF:

0.000815

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000663

Alfa

AF:

0.0000378

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.6570A>T (p.L2190F) alteration is located in exon 30 (coding exon 30) of the TENM1 gene. This alteration results from a A to T substitution at nucleotide position 6570, causing the leucine (L) at amino acid position 2190 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.043

T;T

MetaSVM

Uncertain

0.090

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.058

T;T

Polyphen

1.0

D;.

Vest4

0.27

MutPred

0.30

Gain of sheet (P = 0.0827);.;

MVP

0.58

MPC

0.88

ClinPred

0.20

GERP RS

2.0

Varity_R

0.65

gMVP

0.47

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