rs367782368

chr6-152334285-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_182961.4(SYNE1):c.12529-12G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,612,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: SYNE1 NM_182961.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00009389
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.74

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-152334285-C-T is Benign according to our data. Variant chr6-152334285-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.12529-12G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.12529-12G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.12316-12G>A		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152026 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000948

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000303 AC: 75 AN: 247658 Hom.: 0 AF XY: 0.000276 AC XY: 37 AN XY: 134174

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000783

Gnomad ASJ exome AF: 0.00261

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000153

Gnomad OTH exome AF: 0.000827

GnomAD4 exome AF: 0.000179 AC: 262 AN: 1460356 Hom.: 0 Cov.: 31 AF XY: 0.000167 AC XY: 121 AN XY: 726492

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000783

Gnomad4 ASJ exome AF: 0.00226

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000384

Gnomad4 NFE exome AF: 0.0000998

Gnomad4 OTH exome AF: 0.000563

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74376

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000851

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000948

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000521 Hom.: 0

Bravo AF: 0.000272

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 05, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.6
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000094
dbscSNV1_RF	Benign	0.0060

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

Publications

LitVar

Other links and lift over

dbSNP: rs367782368; hg19: chr6-152655420;