Variant chrX-124381030-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_001163278.2(TENM1):c.7705A>G(p.Asn2569Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,210,203 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

TENM1
NM_001163278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 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=0.16049376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
TENM1	NM_001163278.2 linkuse as main transcript	c.7705A>G	p.Asn2569Asp	missense_variant	35/35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 linkuse as main transcript	c.7702A>G	p.Asn2568Asp	missense_variant	32/32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 linkuse as main transcript	c.7684A>G	p.Asn2562Asp	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.7684A>G	p.Asn2562Asp	missense_variant	31/31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 linkuse as main transcript	c.7651A>G	p.Asn2551Asp	missense_variant	35/35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 linkuse as main transcript	n.454-30792T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

112027

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34189

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000378

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

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182875

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67561

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

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:

0.00000182

AC:

AN:

1098176

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363564

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

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:

0.0000357

AC:

AN:

112027

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34189

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000378

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:

0.00

Bravo

AF:

0.000102

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

Jan 16, 2024

The c.7705A>G (p.N2569D) alteration is located in exon 32 (coding exon 32) of the TENM1 gene. This alteration results from a A to G substitution at nucleotide position 7705, causing the asparagine (N) at amino acid position 2569 to be replaced by an aspartic acid (D). 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

0.073

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.028

T;.

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.86

D;D

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.90

L;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.31

Sift

Benign

0.55

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.0

B;.

Vest4

0.10

MutPred

0.41

Loss of sheet (P = 0.0457);.;

MVP

0.40

MPC

0.53

ClinPred

0.097

GERP RS

5.8

Varity_R

0.41

gMVP

0.79

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