Genetic Variant SYNE1:c.3505-39A>C (chr6-152447661-T-G) – 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.3505-39A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,612,256 control chromosomes in the GnomAD database, including 169,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 22183 hom., cov: 33)

Exomes 𝑓: 0.44 ( 147792 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.462

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=-0.77).

BP6

Variant 6-152447661-T-G is Benign according to our data. Variant chr6-152447661-T-G is described in ClinVar as [Benign]. Clinvar id is 262196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.3505-39A>C		intron_variant	Intron 28 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.3505-39A>C		intron_variant	Intron 28 of 145	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79025

AN:

151992

Hom.:

22143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.720

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.761

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.527

GnomAD3 exomes

AF:

0.472

AC:

118444

AN:

250844

Hom.:

30029

AF XY:

0.474

AC XY:

64252

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.725

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.489

Gnomad EAS exome

AF:

0.765

Gnomad SAS exome

AF:

0.524

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.450

GnomAD4 exome

AF:

0.441

AC:

644357

AN:

1460144

Hom.:

147792

Cov.:

AF XY:

0.444

AC XY:

322677

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.725

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.486

Gnomad4 EAS exome

AF:

0.789

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.402

Gnomad4 NFE exome

AF:

0.417

Gnomad4 OTH exome

AF:

0.472

GnomAD4 genome

AF:

0.520

AC:

79120

AN:

152112

Hom.:

22183

Cov.:

AF XY:

0.518

AC XY:

38549

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.720

Gnomad4 AMR

AF:

0.419

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.761

Gnomad4 SAS

AF:

0.544

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.526

Alfa

AF:

0.489

Hom.:

4447

Bravo

AF:

0.530

Asia WGS

AF:

0.628

AC:

2184

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

-0.77

CADD

Benign

0.51

DANN

Benign

0.76

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