chr6-152538508-G-T

Position:

• chr6-152538508-G-T

Variant summary

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

The NM_182961.4(SYNE1):​c.129+1452C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,660 control chromosomes in the GnomAD database, including 6,788 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 0.28 (6788 hom., cov: 31)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.898

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 (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.129+1452C>A		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.129+1452C>A		intron_variant		1	NM_182961.4	ENSP00000356224	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43125 AN: 151544 Hom.: 6788 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.284 AC: 43144 AN: 151660 Hom.: 6788 Cov.: 31 AF XY: 0.290 AC XY: 21507 AN XY: 74098

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.263

Alfa AF: 0.314 Hom.: 2058

Bravo AF: 0.261

Asia WGS AF: 0.323 AC: 1123 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1405695; hg19: chr6-152859643;