rs763485258

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM5PP3_ModerateBS2

The NM_001098816.3(TENM4):​c.4100C>T​(p.Thr1367Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1367N) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

TENM4
NM_001098816.3 missense

Scores

12
6
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.02
Variant links:
Genes affected
TENM4 (HGNC:29945): (teneurin transmembrane protein 4) The protein encoded by this gene plays a role in establishing proper neuronal connectivity during development. Defects in this gene have been associated with hereditary essential tremor-5. [provided by RefSeq, Oct 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM5
Other missense variant is known to change same aminoacid residue: Variant chr11-78708470-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 219133.Status of the report is no_assertion_criteria_provided, 0 stars.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.871
BS2
High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TENM4NM_001098816.3 linkc.4100C>T p.Thr1367Ile missense_variant Exon 27 of 34 ENST00000278550.12 NP_001092286.2 Q6N022

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TENM4ENST00000278550.12 linkc.4100C>T p.Thr1367Ile missense_variant Exon 27 of 34 5 NM_001098816.3 ENSP00000278550.7 Q6N022

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152246
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248960
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135050
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:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000281
AC:
41
AN:
1461656
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152246
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.52
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.67
D
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.13
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Uncertain
2.9
M
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.0
D
REVEL
Pathogenic
0.80
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.020
D
Polyphen
1.0
D
Vest4
0.90
MutPred
0.54
Gain of sheet (P = 0.0028);
MVP
0.45
MPC
0.75
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.58
gMVP
0.78

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.

Other links and lift over

dbSNP: rs763485258; hg19: chr11-78419515; API