rs9478320

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_182961.4(SYNE1):c.11734-5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,613,580 control chromosomes in the GnomAD database, including 294,813 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26719 hom., cov: 31)

Exomes 𝑓: 0.60 ( 268094 hom. )

Consequence

SYNE1
NM_182961.4 splice_region, intron

Scores

Splicing: ADA: 0.7992

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.420

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-152350340-A-C is Benign according to our data. Variant chr6-152350340-A-C is described in ClinVar as [Benign]. Clinvar id is 263075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152350340-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.11734-5T>G		splice_region_variant, intron_variant	Intron 71 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNE1	ENST00000367255.10 link	c.11734-5T>G	splice_region_variant, intron_variant	Intron 71 of 145	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 link	c.11688+278T>G	intron_variant	Intron 71 of 145	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000471834.1 link	n.4872-5T>G	splice_region_variant, intron_variant	Intron 14 of 18	1

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89913

AN:

151844

Hom.:

26695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.600

GnomAD3 exomes

AF:

0.589

AC:

147870

AN:

250998

Hom.:

43922

AF XY:

0.586

AC XY:

79535

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.566

Gnomad AMR exome

AF:

0.605

Gnomad ASJ exome

AF:

0.647

Gnomad EAS exome

AF:

0.606

Gnomad SAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.605

Gnomad OTH exome

AF:

0.591

GnomAD4 exome

AF:

0.605

AC:

883707

AN:

1461618

Hom.:

268094

Cov.:

AF XY:

0.602

AC XY:

437612

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.560

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.648

Gnomad4 EAS exome

AF:

0.640

Gnomad4 SAS exome

AF:

0.524

Gnomad4 FIN exome

AF:

0.546

Gnomad4 NFE exome

AF:

0.613

Gnomad4 OTH exome

AF:

0.599

GnomAD4 genome

AF:

0.592

AC:

89986

AN:

151962

Hom.:

26719

Cov.:

AF XY:

0.587

AC XY:

43624

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.570

Gnomad4 AMR

AF:

0.617

Gnomad4 ASJ

AF:

0.641

Gnomad4 EAS

AF:

0.622

Gnomad4 SAS

AF:

0.534

Gnomad4 FIN

AF:

0.534

Gnomad4 NFE

AF:

0.609

Gnomad4 OTH

AF:

0.603

Alfa

AF:

0.606

Hom.:

46237

Bravo

AF:

0.598

Asia WGS

AF:

0.598

AC:

2081

AN:

3478

EpiCase

AF:

0.597

EpiControl

AF:

0.594

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type

Benign:2

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

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

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

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

-0.82

CADD

Benign

9.3

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.80

dbscSNV1_RF

Benign

0.18

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