rs73619386

chr6-152236211-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_182961.4(SYNE1):c.20292T>C(p.Asp6764=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,614,180 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SYNE1 NM_182961.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.201

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 6-152236211-A-G is Benign according to our data. Variant chr6-152236211-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 283708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.201 with no splicing effect.
• BS2: High AC in GnomAd at 234 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.20292T>C	p.Asp6764=	synonymous_variant	110/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.20292T>C	p.Asp6764=	synonymous_variant	110/146	1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.20079T>C	p.Asp6693=	synonymous_variant	109/146	1
SYNE1	ENST00000367256.9	n.3984T>C		non_coding_transcript_exon_variant	25/61	1
SYNE1	ENST00000409694.6	n.3876T>C		non_coding_transcript_exon_variant	23/59	1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152206 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000350 AC: 88 AN: 251430 Hom.: 0 AF XY: 0.000272 AC XY: 37 AN XY: 135888

Gnomad AFR exome AF: 0.00486

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000133 AC: 194 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 79 AN XY: 727228

Gnomad4 AFR exome AF: 0.00523

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.00154 AC: 234 AN: 152324 Hom.: 1 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74498

Gnomad4 AFR AF: 0.00527

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000786 Hom.: 0

Bravo AF: 0.00172

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 18, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	SYNE1: BP4, BP7 -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 02, 2015

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	2.1
Dann	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73619386; hg19: chr6-152557346;