6-152362278-G-T

Variant names:

• chr6-152362278-G-T
• rs4407724
• NM_182961.4:c.10191C>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182961.4(SYNE1):​c.10191C>A​(p.Gly3397Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,613,830 control chromosomes in the GnomAD database, including 367,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32077 hom., cov: 32)
  • Exomes 𝑓: 0.68 (335469 hom.)
• Consequence: SYNE1 NM_182961.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.240

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-152362278-G-T is Benign according to our data. Variant chr6-152362278-G-T is described in ClinVar as [Benign]. Clinvar id is 130388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152362278-G-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.10191C>A	p.Gly3397Gly	synonymous_variant	Exon 64 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.10191C>A	p.Gly3397Gly	synonymous_variant	Exon 64 of 146	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.10212C>A	p.Gly3404Gly	synonymous_variant	Exon 64 of 146	1		ENSP00000396024.1
SYNE1	ENST00000471834.1	n.3329C>A		non_coding_transcript_exon_variant	Exon 7 of 19	1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98434 AN: 151898 Hom.: 32056 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.674

GnomAD3 exomes AF: 0.659 AC: 165821 AN: 251456 Hom.: 55170 AF XY: 0.658 AC XY: 89418 AN XY: 135906

Gnomad AFR exome AF: 0.577

Gnomad AMR exome AF: 0.669

Gnomad ASJ exome AF: 0.709

Gnomad EAS exome AF: 0.789

Gnomad SAS exome AF: 0.596

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.676 AC: 988107 AN: 1461814 Hom.: 335469 Cov.: 62 AF XY: 0.674 AC XY: 489812 AN XY: 727218

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 0.710

Gnomad4 EAS exome AF: 0.822

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.648 AC: 98507 AN: 152016 Hom.: 32077 Cov.: 32 AF XY: 0.643 AC XY: 47803 AN XY: 74296

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.676

Alfa AF: 0.665 Hom.: 61556

Bravo AF: 0.652

Asia WGS AF: 0.700 AC: 2437 AN: 3478

EpiCase AF: 0.669

EpiControl AF: 0.662

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:7

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Jan 25, 2016

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. -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 02, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.021
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4407724; hg19: chr6-152683413; COSMIC: COSV54950833; COSMIC: COSV54950833;