rs886044642

chr6-152308637-G-Achr6-152308637-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_182961.4(SYNE1):c.17203-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000556 in 1,327,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00056 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNE1 NM_182961.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006666
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.194

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-152308637-G-A is Benign according to our data. Variant chr6-152308637-G-A is described in ClinVar as [Benign]. Clinvar id is 706436.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-152308637-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.17203-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.17203-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.16994-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1
SYNE1	ENST00000367256.9	n.895-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
SYNE1	ENST00000409694.6	n.787-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 76 AN: 135078 Hom.: 0 Cov.: 25 FAILED QC

Gnomad AFR AF: 0.000750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000306

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00423

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000257

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000556 AC: 738 AN: 1327034 Hom.: 0 Cov.: 37 AF XY: 0.000596 AC XY: 394 AN XY: 661006

Gnomad4 AFR exome AF: 0.00245

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.000514

Gnomad4 EAS exome AF: 0.000196

Gnomad4 SAS exome AF: 0.000870

Gnomad4 FIN exome AF: 0.00180

Gnomad4 NFE exome AF: 0.000400

Gnomad4 OTH exome AF: 0.000819

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000563 AC: 76 AN: 135104 Hom.: 0 Cov.: 25 AF XY: 0.000719 AC XY: 47 AN XY: 65332

Gnomad4 AFR AF: 0.000748

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000306

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00423

Gnomad4 NFE AF: 0.000257

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00349 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.5
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000067

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886044642; hg19: chr6-152629772;