Variant X-124383727-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_001163278.2(TENM1):c.7204C>G(p.Gln2402Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Consequence

TENM1
NM_001163278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.064976454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
TENM1	NM_001163278.2 linkuse as main transcript	c.7204C>G	p.Gln2402Glu	missense_variant	33/35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 linkuse as main transcript	c.7201C>G	p.Gln2401Glu	missense_variant	30/32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 linkuse as main transcript	c.7183C>G	p.Gln2395Glu	missense_variant	29/31	NP_055068.2	Q9UKZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
TENM1	ENST00000371130.7 linkuse as main transcript	c.7183C>G	p.Gln2395Glu	missense_variant	29/31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 linkuse as main transcript	c.7150C>G	p.Gln2384Glu	missense_variant	33/35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 linkuse as main transcript	n.454-28095G>C		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183243

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67781

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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 23, 2024

The c.7204C>G (p.Q2402E) alteration is located in exon 30 (coding exon 30) of the TENM1 gene. This alteration results from a C to G substitution at nucleotide position 7204, causing the glutamine (Q) at amino acid position 2402 to be replaced by a glutamic acid (E). 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

0.065

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.030

T;.

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.0

N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.26

Sift

Benign

0.29

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0

B;.

Vest4

0.11

MutPred

0.39

Loss of methylation at K2394 (P = 0.0926);.;

MVP

0.39

MPC

0.50

ClinPred

0.045

GERP RS

3.8

Varity_R

0.24

gMVP

0.65

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