Variant chr6-152225742-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_182961.4(SYNE1):c.21330C>T(p.Thr7110Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000539 in 1,614,108 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.99

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:

SYNE1 (HGNC:):

SYNE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 6-152225742-G-A is Benign according to our data. Variant chr6-152225742-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152225742-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.99 with no splicing effect.

BS2

High AC in GnomAd4 at 424 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.21330C>T	p.Thr7110Thr	synonymous_variant	116/146	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.21330C>T	p.Thr7110Thr	synonymous_variant	116/146	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00973

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000764

AC:

192

AN:

251420

Hom.:

AF XY:

0.000500

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000305

AC:

446

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000276

AC XY:

201

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.00278

AC:

424

AN:

152268

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

191

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00984

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00327

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	SYNE1: BP4, BS1 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2020	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 16, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

5.1

DANN

Benign

0.48

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