rs1322512

Variant names:

• chr6-152626818-C-A
• rs1322512
• NM_182961.4:c.67+1447G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152626818-C-A
• chr6-152626818-C-G
• chr6-152626818-C-T

Variant summary

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

The NM_182961.4(SYNE1):​c.67+1447G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 151,998 control chromosomes in the GnomAD database, including 34,887 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 0.68 (34887 hom., cov: 32)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 14 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.67+1447G>T		intron_variant	Intron 3 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.67+1447G>T		intron_variant	Intron 3 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102813 AN: 151880 Hom.: 34894 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.677 AC: 102845 AN: 151998 Hom.: 34887 Cov.: 32 AF XY: 0.669 AC XY: 49678 AN XY: 74276

African (AFR) AF: 0.678 AC: 28095 AN: 41440

American (AMR) AF: 0.640 AC: 9771 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2281 AN: 3468

East Asian (EAS) AF: 0.656 AC: 3388 AN: 5166

South Asian (SAS) AF: 0.589 AC: 2839 AN: 4820

European-Finnish (FIN) AF: 0.597 AC: 6306 AN: 10558

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47943 AN: 67962

Other (OTH) AF: 0.679 AC: 1431 AN: 2108

Alfa AF: 0.694 Hom.: 75321

Bravo AF: 0.683

Asia WGS AF: 0.582 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.52
DANN	Benign	0.65
PhyloP100		-0.25
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: rs1322512; hg19: chr6-152947953;