rs2623968

Variant names:

• chr6-152516177-A-G
• rs2623968
• NM_182961.4:c.309+4282T>C

Variant summary

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

The NM_182961.4(SYNE1):​c.309+4282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,006 control chromosomes in the GnomAD database, including 28,124 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 0.60 (28124 hom., cov: 31)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.309+4282T>C		intron_variant	Intron 6 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.309+4282T>C		intron_variant	Intron 6 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91055 AN: 151888 Hom.: 28096 Cov.: 31

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.600 AC: 91131 AN: 152006 Hom.: 28124 Cov.: 31 AF XY: 0.601 AC XY: 44617 AN XY: 74264

African (AFR) AF: 0.725 AC: 30085 AN: 41472

American (AMR) AF: 0.459 AC: 7002 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3902 AN: 5160

South Asian (SAS) AF: 0.537 AC: 2582 AN: 4812

European-Finnish (FIN) AF: 0.658 AC: 6935 AN: 10546

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37080 AN: 67962

Other (OTH) AF: 0.560 AC: 1182 AN: 2110

Alfa AF: 0.571 Hom.: 6619

Bravo AF: 0.592

Asia WGS AF: 0.625 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.36
PhyloP100		-0.22
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: rs2623968; hg19: chr6-152837312;