6-152469438-G-T

Variant names:

• chr6-152469438-G-T
• rs9371601
• NM_182961.4:c.1632+2159C>A

Variant summary

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

The NM_182961.4(SYNE1):​c.1632+2159C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,618 control chromosomes in the GnomAD database, including 18,037 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 0.46 (18037 hom., cov: 30)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 51 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=-0.97).
• 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.1632+2159C>A		intron_variant	Intron 16 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.1632+2159C>A		intron_variant	Intron 16 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69843 AN: 151500 Hom.: 18011 Cov.: 30

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.461 AC: 69917 AN: 151618 Hom.: 18037 Cov.: 30 AF XY: 0.461 AC XY: 34161 AN XY: 74084

African (AFR) AF: 0.682 AC: 28197 AN: 41342

American (AMR) AF: 0.363 AC: 5526 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3871 AN: 5122

South Asian (SAS) AF: 0.495 AC: 2373 AN: 4796

European-Finnish (FIN) AF: 0.335 AC: 3510 AN: 10488

Middle Eastern (MID) AF: 0.479 AC: 139 AN: 290

European-Non Finnish (NFE) AF: 0.350 AC: 23748 AN: 67876

Other (OTH) AF: 0.452 AC: 952 AN: 2106

Alfa AF: 0.384 Hom.: 33056

Bravo AF: 0.474

Asia WGS AF: 0.589 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
DANN	Benign	0.31
PhyloP100		-0.78
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: rs9371601; hg19: chr6-152790573;