rs13211987

Positions:

• chr6-152134963-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182961.4(SYNE1):​c.25788+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,089,152 control chromosomes in the GnomAD database, including 10,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1039 hom., cov: 32)
  • Exomes 𝑓: 0.13 (8995 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.199

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-152134963-G-A is Benign according to our data. Variant chr6-152134963-G-A is described in ClinVar as [Benign]. Clinvar id is 1246008.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	Protein	UniProt
SYNE1	NM_001347702.2	c.2322+141C>T		intron_variant		ENST00000354674.5	NP_001334631.1
SYNE1	NM_182961.4	c.25788+141C>T		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000354674.5	c.2322+141C>T		intron_variant		5	NM_001347702.2	ENSP00000346701
SYNE1	ENST00000367255.10	c.25788+141C>T		intron_variant		1	NM_182961.4	ENSP00000356224	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15842 AN: 151824 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0825

GnomAD4 exome AF: 0.133 AC: 124456 AN: 937208 Hom.: 8995 Cov.: 12 AF XY: 0.131 AC XY: 62981 AN XY: 480850

Gnomad4 AFR exome AF: 0.0371

Gnomad4 AMR exome AF: 0.0443

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0880

Gnomad4 SAS exome AF: 0.0860

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.104 AC: 15853 AN: 151944 Hom.: 1039 Cov.: 32 AF XY: 0.103 AC XY: 7648 AN XY: 74264

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.0579

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0602

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0849

Alfa AF: 0.121 Hom.: 194

Bravo AF: 0.0896

Asia WGS AF: 0.0890 AC: 313 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.86
DANN	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13211987; hg19: chr6-152456098; COSMIC: COSV55015752;