NM_182961.4:c.68-4400T>C

Variant names:

• chr6-152544421-A-G
• rs1358317
• NM_182961.4:c.68-4400T>C

Variant summary

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

The NM_182961.4(SYNE1):​c.68-4400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,992 control chromosomes in the GnomAD database, including 5,061 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 0.25 (5061 hom., cov: 32)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.68-4400T>C		intron_variant	Intron 3 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.68-4400T>C		intron_variant	Intron 3 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38083 AN: 151874 Hom.: 5055 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.251 AC: 38126 AN: 151992 Hom.: 5061 Cov.: 32 AF XY: 0.248 AC XY: 18431 AN XY: 74286

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.254

Alfa AF: 0.233 Hom.: 1078

Bravo AF: 0.258

Asia WGS AF: 0.289 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1358317; hg19: chr6-152865556;