6-152344168-C-T

Position:

chr6-152344168-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000367255.10(SYNE1):c.12138G>A(p.Gln4046=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,614,214 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 142 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 147 hom. )

Consequence

SYNE1
ENST00000367255.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.219

Variant links:

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]

SYNE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 6-152344168-C-T is Benign according to our data. Variant chr6-152344168-C-T is described in ClinVar as [Benign]. Clinvar id is 130396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152344168-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.219 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.12138G>A	p.Gln4046=	synonymous_variant	74/146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.12138G>A	p.Gln4046=	synonymous_variant	74/146	1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.11925G>A	p.Gln3975=	synonymous_variant	73/146	1		ENSP00000396024
SYNE1	ENST00000471834.1 linkuse as main transcript	n.5276G>A		non_coding_transcript_exon_variant	17/19	1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3805

AN:

152206

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.00729

AC:

1833

AN:

251484

Hom.:

AF XY:

0.00601

AC XY:

817

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0822

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.0186

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000993

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00332

AC:

4850

AN:

1461890

Hom.:

147

Cov.:

AF XY:

0.00303

AC XY:

2202

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0889

Gnomad4 AMR exome

AF:

0.00478

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000556

Gnomad4 OTH exome

AF:

0.00778

GnomAD4 genome

AF:

0.0251

AC:

3816

AN:

152324

Hom.:

142

Cov.:

AF XY:

0.0244

AC XY:

1816

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0846

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.0274

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00166

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 18, 2016	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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 25, 2019

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.5

DANN

Benign

0.61

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over