6-152201677-T-G

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.23145+147A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,103,282 control chromosomes in the GnomAD database, including 185,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26078 hom., cov: 31)
  • Exomes 𝑓: 0.58 (159530 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13

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=-0.87).
• BP6: Variant 6-152201677-T-G is Benign according to our data. Variant chr6-152201677-T-G is described in ClinVar as [Benign]. Clinvar id is 670211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.23145+147A>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.23145+147A>C		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88537 AN: 151838 Hom.: 26042 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.576 AC: 547740 AN: 951326 Hom.: 159530 AF XY: 0.576 AC XY: 281150 AN XY: 488386

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.676

Gnomad4 ASJ exome AF: 0.594

Gnomad4 EAS exome AF: 0.644

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.583 AC: 88637 AN: 151956 Hom.: 26078 Cov.: 31 AF XY: 0.579 AC XY: 42992 AN XY: 74288

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.615

Alfa AF: 0.584 Hom.: 54105

Bravo AF: 0.600

Asia WGS AF: 0.608 AC: 2114 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 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.32
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: rs2673776; hg19: chr6-152522812; COSMIC: COSV54945498;