6-152401093-A-G

Variant names:

• chr6-152401093-A-G
• rs177330
• NM_182961.4:c.7029+45T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.7029+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,581,814 control chromosomes in the GnomAD database, including 131,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15834 hom., cov: 32)
  • Exomes 𝑓: 0.39 (115919 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.00200

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-152401093-A-G is Benign according to our data. Variant chr6-152401093-A-G is described in ClinVar as [Benign]. Clinvar id is 262198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.7029+45T>C		intron_variant	Intron 47 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.7029+45T>C		intron_variant	Intron 47 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.7050+45T>C		intron_variant	Intron 47 of 145	1		ENSP00000396024.1
SYNE1	ENST00000461872.6	n.7247+45T>C		intron_variant	Intron 45 of 54	1
SYNE1	ENST00000535081.1	n.*210T>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67323 AN: 151936 Hom.: 15820 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.437

GnomAD3 exomes AF: 0.423 AC: 104729 AN: 247766 Hom.: 23921 AF XY: 0.425 AC XY: 57033 AN XY: 134046

Gnomad AFR exome AF: 0.567

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.767

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.395

GnomAD4 exome AF: 0.393 AC: 562513 AN: 1429760 Hom.: 115919 Cov.: 25 AF XY: 0.397 AC XY: 282898 AN XY: 713442

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.776

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.443 AC: 67385 AN: 152054 Hom.: 15834 Cov.: 32 AF XY: 0.446 AC XY: 33128 AN XY: 74310

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.436

Alfa AF: 0.414 Hom.: 3821

Bravo AF: 0.445

Asia WGS AF: 0.587 AC: 2042 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Arthrogryposis multiplex congenita 3, myogenic type Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs177330; hg19: chr6-152722228;