chr11-78658368-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_001098816.3(TENM4):ā€‹c.8000A>Gā€‹(p.Gln2667Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000691 in 1,614,024 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0037 ( 2 hom., cov: 33)
Exomes š‘“: 0.00038 ( 4 hom. )

Consequence

TENM4
NM_001098816.3 missense

Scores

9
9

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.00
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 Benign. Variant got -15 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TENM4. . Gene score misZ 2.7323 (greater than the threshold 3.09). Trascript score misZ 3.5261 (greater than threshold 3.09). GenCC has associacion of gene with tremor, hereditary essential, 5.
BP4
Computational evidence support a benign effect (MetaRNN=0.0096925795).
BP6
Variant 11-78658368-T-C is Benign according to our data. Variant chr11-78658368-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 786205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 562 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TENM4NM_001098816.3 linkuse as main transcriptc.8000A>G p.Gln2667Arg missense_variant 34/34 ENST00000278550.12 NP_001092286.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TENM4ENST00000278550.12 linkuse as main transcriptc.8000A>G p.Gln2667Arg missense_variant 34/345 NM_001098816.3 ENSP00000278550 P1
TENM4ENST00000530738.1 linkuse as main transcriptc.2801-314A>G intron_variant 2 ENSP00000431711

Frequencies

GnomAD3 genomes
AF:
0.00369
AC:
562
AN:
152246
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0125
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
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:
0.000118
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00102
AC:
255
AN:
249024
Hom.:
2
AF XY:
0.000814
AC XY:
110
AN XY:
135104
show subpopulations
Gnomad AFR exome
AF:
0.0128
Gnomad AMR exome
AF:
0.00125
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:
0.0000532
Gnomad OTH exome
AF:
0.00132
GnomAD4 exome
AF:
0.000378
AC:
553
AN:
1461660
Hom.:
4
Cov.:
31
AF XY:
0.000326
AC XY:
237
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.0122
Gnomad4 AMR exome
AF:
0.00116
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:
0.0000468
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
AF:
0.00369
AC:
562
AN:
152364
Hom.:
2
Cov.:
33
AF XY:
0.00380
AC XY:
283
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0124
Gnomad4 AMR
AF:
0.00202
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.000683
Hom.:
2
Bravo
AF:
0.00403
ESP6500AA
AF:
0.0120
AC:
51
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00123
AC:
149
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2024TENM4: BS1 -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.80
T
MetaRNN
Benign
0.0097
T
MetaSVM
Uncertain
0.18
D
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.53
Sift
Benign
0.76
T
Sift4G
Uncertain
0.0050
D
Polyphen
0.99
D
Vest4
0.19
MVP
0.25
MPC
0.31
ClinPred
0.037
T
GERP RS
5.6
Varity_R
0.36
gMVP
0.59

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: rs78572681; hg19: chr11-78369413; COSMIC: COSV99074590; API