dbSNP rs9371581: SYNE1:c.17346+38C>T (chr6-152308451-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_182961.4(SYNE1):c.17346+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,612,054 control chromosomes in the GnomAD database, including 220,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18551 hom., cov: 31)

Exomes 𝑓: 0.52 ( 201678 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.48

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=-0.78).

BP6

Variant 6-152308451-G-A is Benign according to our data. Variant chr6-152308451-G-A is described in ClinVar as [Benign]. Clinvar id is 262172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.17346+38C>T		intron_variant	Intron 91 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNE1	ENST00000367255.10 link	c.17346+38C>T	intron_variant	Intron 91 of 145	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 link	c.17133+38C>T	intron_variant	Intron 90 of 145	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000367256.9 link	n.1038+38C>T	intron_variant	Intron 6 of 60	1
SYNE1	ENST00000409694.6 link	n.930+38C>T	intron_variant	Intron 4 of 58	1

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73241

AN:

151830

Hom.:

18550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.745

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.455

GnomAD3 exomes

AF:

0.505

AC:

126889

AN:

251272

Hom.:

33336

AF XY:

0.502

AC XY:

68177

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.464

Gnomad EAS exome

AF:

0.641

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.689

Gnomad NFE exome

AF:

0.533

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.521

AC:

761057

AN:

1460106

Hom.:

201678

Cov.:

AF XY:

0.518

AC XY:

376310

AN XY:

726428

show subpopulations

Gnomad4 AFR exome

AF:

0.328

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.464

Gnomad4 EAS exome

AF:

0.635

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.679

Gnomad4 NFE exome

AF:

0.533

Gnomad4 OTH exome

AF:

0.506

GnomAD4 genome

AF:

0.482

AC:

73275

AN:

151948

Hom.:

18551

Cov.:

AF XY:

0.488

AC XY:

36215

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.437

Gnomad4 ASJ

AF:

0.464

Gnomad4 EAS

AF:

0.647

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.696

Gnomad4 NFE

AF:

0.538

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.514

Hom.:

42669

Bravo

AF:

0.459

Asia WGS

AF:

0.501

AC:

1745

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 14, 2018

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. -

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

- -

Autosomal recessive ataxia, Beauce 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

-0.78

CADD

Benign

1.5

DANN

Benign

0.84

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