6-152149001-T-C

Variant names:

• chr6-152149001-T-C
• rs718527
• NM_182961.4:c.24642+476A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182961.4(SYNE1):​c.24642+476A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,868 control chromosomes in the GnomAD database, including 26,595 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26595 hom., cov: 31)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive ataxia, Beauce type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Orphanet, PanelApp Australia, G2P
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive myogenic arthrogryposis multiplex congenita

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000300811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.24642+476A>G		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_001347702.2	MANE Plus Clinical	c.1107+476A>G		intron	N/A	NP_001334631.1	F8WAI0
	SYNE1	NM_033071.5		c.24429+476A>G		intron	N/A	NP_149062.2	Q8NF91-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.24642+476A>G		intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000354674.5	TSL:5 MANE Plus Clinical	c.1107+476A>G		intron	N/A	ENSP00000346701.4	F8WAI0
	SYNE1	ENST00000423061.6	TSL:1	c.24429+476A>G		intron	N/A	ENSP00000396024.1	A0A0C4DG40

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89218 AN: 151748 Hom.: 26544 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.599

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.588 AC: 89339 AN: 151868 Hom.: 26595 Cov.: 31 AF XY: 0.590 AC XY: 43748 AN XY: 74204

African (AFR) AF: 0.657 AC: 27203 AN: 41428

American (AMR) AF: 0.658 AC: 10040 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2007 AN: 3464

East Asian (EAS) AF: 0.690 AC: 3550 AN: 5142

South Asian (SAS) AF: 0.677 AC: 3256 AN: 4812

European-Finnish (FIN) AF: 0.462 AC: 4856 AN: 10516

Middle Eastern (MID) AF: 0.521 AC: 151 AN: 290

European-Non Finnish (NFE) AF: 0.538 AC: 36564 AN: 67928

Other (OTH) AF: 0.602 AC: 1271 AN: 2110

Alfa AF: 0.556 Hom.: 24397

Bravo AF: 0.606

Asia WGS AF: 0.687 AC: 2388 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0020
DANN	Benign	0.31
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs718527; hg19: chr6-152470136; COSMIC: COSV54938513; COSMIC: COSV54938513;