rs527822279

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182961.4(SYNE1):​c.8984T>G​(p.Ile2995Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

SYNE1
NM_182961.4 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.95
Variant links:
Genes affected
SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
SYNE1-AS1 (HGNC:40793): (SYNE1 antisense RNA 1)

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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;
BP4
Computational evidence support a benign effect (MetaRNN=0.31550395).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNE1NM_182961.4 linkc.8984T>G p.Ile2995Arg missense_variant Exon 56 of 146 ENST00000367255.10 NP_892006.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNE1ENST00000367255.10 linkc.8984T>G p.Ile2995Arg missense_variant Exon 56 of 146 1 NM_182961.4 ENSP00000356224.5 Q8NF91-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.56
D;.;T;T
Eigen
Benign
0.0011
Eigen_PC
Benign
0.036
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
2.0
M;.;.;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.9
N;.;N;.
REVEL
Benign
0.20
Sift
Uncertain
0.0090
D;.;D;.
Sift4G
Uncertain
0.014
D;D;D;D
Polyphen
0.52
P;.;.;.
Vest4
0.47
MutPred
0.53
Gain of disorder (P = 0.0172);.;.;.;
MVP
0.65
MPC
0.59
ClinPred
0.90
D
GERP RS
4.9
Varity_R
0.15
gMVP
0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-152702166; API