6-152309862-G-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_182961.4(SYNE1):​c.17175C>T​(p.Thr5725Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,982 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 2 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -8.32

Publications

3 publications found
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 Gene-Disease associations (from GenCC):
  • autosomal recessive ataxia, Beauce type
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
  • arthrogryposis multiplex congenita 3, myogenic type
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • Emery-Dreifuss muscular dystrophy 4, autosomal dominant
    Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
  • autosomal dominant Emery-Dreifuss muscular dystrophy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • autosomal recessive myogenic arthrogryposis multiplex congenita
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 6-152309862-G-A is Benign according to our data. Variant chr6-152309862-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 388578. Variant chr6-152309862-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 388578. Variant chr6-152309862-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 388578. Variant chr6-152309862-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 388578.
BP7
Synonymous conserved (PhyloP=-8.32 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNE1NM_182961.4 linkc.17175C>T p.Thr5725Thr synonymous_variant Exon 90 of 146 ENST00000367255.10 NP_892006.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNE1ENST00000367255.10 linkc.17175C>T p.Thr5725Thr synonymous_variant Exon 90 of 146 1 NM_182961.4 ENSP00000356224.5 Q8NF91-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152146
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00251
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000479
GnomAD2 exomes
AF:
0.000187
AC:
47
AN:
251312
AF XY:
0.000177
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00190
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000104
AC:
152
AN:
1461718
Hom.:
2
Cov.:
31
AF XY:
0.0000990
AC XY:
72
AN XY:
727166
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.000112
AC:
5
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00134
AC:
53
AN:
39698
South Asian (SAS)
AF:
0.000394
AC:
34
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53262
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.0000441
AC:
49
AN:
1112006
Other (OTH)
AF:
0.000166
AC:
10
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.459
Heterozygous variant carriers
0
9
19
28
38
47
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152264
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74448
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41560
American (AMR)
AF:
0.0000654
AC:
1
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00251
AC:
13
AN:
5174
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68022
Other (OTH)
AF:
0.000474
AC:
1
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.543
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.000136
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1
Aug 10, 2017
Eurofins Ntd Llc (ga)
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
Aug 24, 2016
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Nov 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.70
DANN
Benign
0.82
PhyloP100
-8.3
Mutation Taster
=93/7
polymorphism

Splicing

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

Publications

Other links and lift over

dbSNP: rs200002217; hg19: chr6-152630997; COSMIC: COSV55070560; API