rs17082664

Variant names:

• chr6-152417619-A-G
• rs17082664
• NM_182961.4:c.5422-604T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-152417619-A-G
• chr6-152417619-A-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.5422-604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,190 control chromosomes in the GnomAD database, including 2,686 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 0.17 (2686 hom., cov: 33)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.5422-604T>C		intron_variant	Intron 40 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.5422-604T>C		intron_variant	Intron 40 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.5443-604T>C		intron_variant	Intron 40 of 145	1		ENSP00000396024.1
SYNE1	ENST00000461872.6	n.5640-604T>C		intron_variant	Intron 38 of 54	1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26547 AN: 152072 Hom.: 2683 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.175 AC: 26571 AN: 152190 Hom.: 2686 Cov.: 33 AF XY: 0.176 AC XY: 13120 AN XY: 74400

African (AFR) AF: 0.254 AC: 10541 AN: 41524

American (AMR) AF: 0.127 AC: 1948 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1896 AN: 5182

South Asian (SAS) AF: 0.173 AC: 836 AN: 4832

European-Finnish (FIN) AF: 0.164 AC: 1734 AN: 10562

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8640 AN: 68010

Other (OTH) AF: 0.157 AC: 332 AN: 2112

Alfa AF: 0.0741 Hom.: 103

Bravo AF: 0.175

Asia WGS AF: 0.249 AC: 863 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.79
PhyloP100		1.2
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: rs17082664; hg19: chr6-152738754;