rs886044642

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_182961.4(SYNE1):​c.17203-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000556 in 1,327,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 25)
Exomes 𝑓: 0.00056 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SYNE1
NM_182961.4 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00006666
1

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.194
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 6-152308637-G-A is Benign according to our data. Variant chr6-152308637-G-A is described in ClinVar as [Benign]. Clinvar id is 706436.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-152308637-G-A is described in Lovd as [Likely_benign].
BS2
High AC in GnomAdExome4 at 738 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SYNE1NM_182961.4 linkuse as main transcriptc.17203-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000367255.10 NP_892006.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYNE1ENST00000367255.10 linkuse as main transcriptc.17203-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_182961.4 ENSP00000356224 P1Q8NF91-1
SYNE1ENST00000423061.6 linkuse as main transcriptc.16994-9C>T splice_polypyrimidine_tract_variant, intron_variant 1 ENSP00000396024
SYNE1ENST00000367256.9 linkuse as main transcriptn.895-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 1
SYNE1ENST00000409694.6 linkuse as main transcriptn.787-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
76
AN:
135078
Hom.:
0
Cov.:
25
FAILED QC
Gnomad AFR
AF:
0.000750
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000306
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00423
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000257
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000556
AC:
738
AN:
1327034
Hom.:
0
Cov.:
37
AF XY:
0.000596
AC XY:
394
AN XY:
661006
show subpopulations
Gnomad4 AFR exome
AF:
0.00245
Gnomad4 AMR exome
AF:
0.00132
Gnomad4 ASJ exome
AF:
0.000514
Gnomad4 EAS exome
AF:
0.000196
Gnomad4 SAS exome
AF:
0.000870
Gnomad4 FIN exome
AF:
0.00180
Gnomad4 NFE exome
AF:
0.000400
Gnomad4 OTH exome
AF:
0.000819
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000563
AC:
76
AN:
135104
Hom.:
0
Cov.:
25
AF XY:
0.000719
AC XY:
47
AN XY:
65332
show subpopulations
Gnomad4 AFR
AF:
0.000748
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000306
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00423
Gnomad4 NFE
AF:
0.000257
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00349
Hom.:
0

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Likely benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 09, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
6.5
DANN
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000067

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: rs886044642; hg19: chr6-152629772; API