Variant chrX-124380878-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001163278.2(TENM1):c.7857G>C(p.Leu2619Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,019 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

TENM1
NM_001163278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.763

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 Uncertain_significance. 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=0.17682356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
TENM1	NM_001163278.2 linkuse as main transcript	c.7857G>C	p.Leu2619Phe	missense_variant	35/35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 linkuse as main transcript	c.7854G>C	p.Leu2618Phe	missense_variant	32/32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 linkuse as main transcript	c.7836G>C	p.Leu2612Phe	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.7836G>C	p.Leu2612Phe	missense_variant	31/31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 linkuse as main transcript	c.7803G>C	p.Leu2601Phe	missense_variant	35/35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 linkuse as main transcript	n.454-30944C>G		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183125

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67699

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

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:

0.00000273

AC:

AN:

1098019

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363415

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000993

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

Cov.:

Bravo

AF:

0.0000416

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

Oct 03, 2024

The c.7857G>C (p.L2619F) alteration is located in exon 32 (coding exon 32) of the TENM1 gene. This alteration results from a G to C substitution at nucleotide position 7857, causing the leucine (L) at amino acid position 2619 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

0.097

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.056

T;.

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

D;D

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.25

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.011

D;D

Polyphen

0.68

P;.

Vest4

0.037

MutPred

0.27

Gain of catalytic residue at L2612 (P = 0.0045);.;

MVP

0.66

MPC

0.60

ClinPred

0.23

GERP RS

4.9

Varity_R

0.28

gMVP

0.25

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