6-152135893-C-A

Position:

• chr6-152135893-C-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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=-0.89).
• 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
SYNE1	NM_001347702.2	c.2194-661G>T		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.25660-661G>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.2194-661G>T		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.25660-661G>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18256 AN: 152010 Hom.: 1197 Cov.: 32

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

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

Other links and lift over

dbSNP: rs6934016; hg19: chr6-152457028;