chr6-152499260-G-C

Position:

• chr6-152499260-G-C

Variant summary

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

The NM_182961.4(SYNE1):​c.889-468C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,800 control chromosomes in the GnomAD database, including 3,142 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 0.20 (3142 hom., cov: 32)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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]

SYNE1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.889-468C>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.889-468C>G		intron_variant		1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29978 AN: 151682 Hom.: 3143 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.198 AC: 29998 AN: 151800 Hom.: 3142 Cov.: 32 AF XY: 0.197 AC XY: 14613 AN XY: 74162

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.221

Alfa AF: 0.128 Hom.: 222

Bravo AF: 0.196

Asia WGS AF: 0.275 AC: 955 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2623963; hg19: chr6-152820395;