rs9322361

chr6-152138008-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182961.4(SYNE1):c.25459-1190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,126 control chromosomes in the GnomAD database, including 1,297 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 (1297 hom., cov: 32)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.1993-1190T>C		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.25459-1190T>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1993-1190T>C		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.25459-1190T>C		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17581 AN: 152008 Hom.: 1299 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17569 AN: 152126 Hom.: 1297 Cov.: 32 AF XY: 0.114 AC XY: 8498 AN XY: 74356

Gnomad4 AFR AF: 0.0315

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.0504

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.128

Alfa AF: 0.154 Hom.: 2679

Bravo AF: 0.108

Asia WGS AF: 0.0510 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.3
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9322361; hg19: chr6-152459143;