chr6-152201238-G-C

Position:

• chr6-152201238-G-C

Variant summary

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

The ENST00000367255.10(SYNE1):​c.23145+586C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,902 control chromosomes in the GnomAD database, including 25,803 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 0.58 (25803 hom., cov: 31)
• Consequence: SYNE1 ENST00000367255.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.23145+586C>G		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.23145+586C>G		intron_variant		1	NM_182961.4	ENSP00000356224	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88064 AN: 151784 Hom.: 25767 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.580 AC: 88164 AN: 151902 Hom.: 25803 Cov.: 31 AF XY: 0.576 AC XY: 42763 AN XY: 74216

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.613

Alfa AF: 0.450 Hom.: 1144

Bravo AF: 0.603

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.013
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs719764; hg19: chr6-152522373;