rs10484863

Variant names:

• chr6-152142353-C-T
• rs10484863
• NM_182961.4:c.25120-1024G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182961.4(SYNE1):​c.25120-1024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 152,004 control chromosomes in the GnomAD database, including 774 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 0.082 (774 hom., cov: 33)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 4 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: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.25120-1024G>A		intron_variant	Intron 138 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2	c.1654-1024G>A		intron_variant	Intron 10 of 17	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.25120-1024G>A		intron_variant	Intron 138 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5	c.1654-1024G>A		intron_variant	Intron 10 of 17	5	NM_001347702.2	ENSP00000346701.4

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12460 AN: 151888 Hom.: 777 Cov.: 33

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0930

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

GnomAD4 genome AF: 0.0819 AC: 12455 AN: 152004 Hom.: 774 Cov.: 33 AF XY: 0.0859 AC XY: 6382 AN XY: 74306

African (AFR) AF: 0.0235 AC: 974 AN: 41460

American (AMR) AF: 0.119 AC: 1819 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1575 AN: 5164

South Asian (SAS) AF: 0.163 AC: 785 AN: 4802

European-Finnish (FIN) AF: 0.0931 AC: 981 AN: 10538

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5944 AN: 67992

Other (OTH) AF: 0.0925 AC: 195 AN: 2108

Alfa AF: 0.0878 Hom.: 1539

Bravo AF: 0.0827

Asia WGS AF: 0.191 AC: 665 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		1.0
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: rs10484863; hg19: chr6-152463488;