6-152135893-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182961.4(SYNE1):​c.25660-661G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,128 control chromosomes in the GnomAD database, including 1,206 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1206 hom., cov: 32)

Consequence

SYNE1
NM_182961.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.215
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SYNE1NM_001347702.2 linkuse as main transcriptc.2194-661G>T intron_variant ENST00000354674.5
SYNE1NM_182961.4 linkuse as main transcriptc.25660-661G>T intron_variant ENST00000367255.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SYNE1ENST00000354674.5 linkuse as main transcriptc.2194-661G>T intron_variant 5 NM_001347702.2
SYNE1ENST00000367255.10 linkuse as main transcriptc.25660-661G>T intron_variant 1 NM_182961.4 P1Q8NF91-1

Frequencies

GnomAD3 genomes
AF:
0.120
AC:
18256
AN:
152010
Hom.:
1197
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0973
Gnomad AMI
AF:
0.138
Gnomad AMR
AF:
0.0645
Gnomad ASJ
AF:
0.111
Gnomad EAS
AF:
0.0588
Gnomad SAS
AF:
0.0872
Gnomad FIN
AF:
0.192
Gnomad MID
AF:
0.0380
Gnomad NFE
AF:
0.144
Gnomad OTH
AF:
0.0909
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.120
AC:
18308
AN:
152128
Hom.:
1206
Cov.:
32
AF XY:
0.119
AC XY:
8863
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0980
Gnomad4 AMR
AF:
0.0643
Gnomad4 ASJ
AF:
0.111
Gnomad4 EAS
AF:
0.0590
Gnomad4 SAS
AF:
0.0871
Gnomad4 FIN
AF:
0.192
Gnomad4 NFE
AF:
0.144
Gnomad4 OTH
AF:
0.0971
Alfa
AF:
0.128
Hom.:
2309
Bravo
AF:
0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.35
DANN
Benign
0.38

Splicing

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: rs6934016; hg19: chr6-152457028; API