Variant chr6-152309811-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.17202+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,612,526 control chromosomes in the GnomAD database, including 10,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 1032 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9323 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.03

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-152309811-C-T is Benign according to our data. Variant chr6-152309811-C-T is described in ClinVar as [Benign]. Clinvar id is 262171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152309811-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.233 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.17202+24G>A		intron_variant		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.17202+24G>A		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.0977

AC:

14857

AN:

152130

Hom.:

1038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0471

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.0856

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.132

AC:

33061

AN:

250328

Hom.:

3285

AF XY:

0.127

AC XY:

17222

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.0449

Gnomad AMR exome

AF:

0.331

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0894

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.0782

Gnomad NFE exome

AF:

0.0957

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.101

AC:

147696

AN:

1460276

Hom.:

9323

Cov.:

AF XY:

0.102

AC XY:

73965

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.0444

Gnomad4 AMR exome

AF:

0.322

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.0796

Gnomad4 NFE exome

AF:

0.0892

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0976

AC:

14861

AN:

152250

Hom.:

1032

Cov.:

AF XY:

0.101

AC XY:

7538

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0472

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.0856

Gnomad4 NFE

AF:

0.0927

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.108

Hom.:

679

Bravo

AF:

0.109

Asia WGS

AF:

0.132

AC:

457

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 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 31, 2024

- -

Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

DANN

Benign

0.57

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