Variant X-124383921-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_001163278.2(TENM1):c.7010G>A(p.Arg2337Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000562 in 1,209,542 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 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 0.000072 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000055 ( 0 hom. 21 hem. )

Consequence

TENM1
NM_001163278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70

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 -4 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=0.3331819).

BS2

High Hemizygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
TENM1	NM_001163278.2 linkuse as main transcript	c.7010G>A	p.Arg2337Gln	missense_variant	33/35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 linkuse as main transcript	c.7007G>A	p.Arg2336Gln	missense_variant	30/32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 linkuse as main transcript	c.6989G>A	p.Arg2330Gln	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.6989G>A	p.Arg2330Gln	missense_variant	29/31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 linkuse as main transcript	c.6956G>A	p.Arg2319Gln	missense_variant	33/35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 linkuse as main transcript	n.454-27901C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000715

AC:

AN:

111873

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

34053

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000753

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000328

AC:

AN:

182805

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67501

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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:

0.0000492

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1097669

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363065

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000677

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000715

AC:

AN:

111873

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

34053

show subpopulations

Gnomad4 AFR

AF:

0.000130

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000753

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Jul 14, 2022

The c.7010G>A (p.R2337Q) alteration is located in exon 30 (coding exon 30) of the TENM1 gene. This alteration results from a G to A substitution at nucleotide position 7010, causing the arginine (R) at amino acid position 2337 to be replaced by a glutamine (Q). 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

0.076

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.029

T;.

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

D;D

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.33

T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.64

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.067

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.97

D;.

Vest4

0.25

MVP

0.66

MPC

0.75

ClinPred

0.085

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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