6-152481162-T-C

Variant names:

• chr6-152481162-T-C
• rs7763880
• NM_182961.4:c.1350+1923A>G

Variant summary

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

The NM_182961.4(SYNE1):​c.1350+1923A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 206,248 control chromosomes in the GnomAD database, including 27,940 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 0.52 (22340 hom., cov: 31)
  • Exomes 𝑓: 0.43 (5600 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 6 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 (MetaRNN=0.0034042597).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.1350+1923A>G		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.1371+1923A>G		intron	N/A	NP_149062.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.1350+1923A>G		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.1371+1923A>G		intron	N/A	ENSP00000396024.1
	SYNE1	ENST00000466159.6	TSL:1	c.1350+1923A>G		intron	N/A	ENSP00000446021.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78973 AN: 151830 Hom.: 22295 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.426 AC: 23119 AN: 54300 Hom.: 5600 Cov.: 0 AF XY: 0.432 AC XY: 12456 AN XY: 28854

African (AFR) AF: 0.717 AC: 767 AN: 1070

American (AMR) AF: 0.353 AC: 1249 AN: 3538

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 519 AN: 1116

East Asian (EAS) AF: 0.770 AC: 2094 AN: 2720

South Asian (SAS) AF: 0.492 AC: 3814 AN: 7752

European-Finnish (FIN) AF: 0.371 AC: 856 AN: 2310

Middle Eastern (MID) AF: 0.469 AC: 76 AN: 162

European-Non Finnish (NFE) AF: 0.383 AC: 12621 AN: 32938

Other (OTH) AF: 0.417 AC: 1123 AN: 2694

GnomAD4 genome AF: 0.520 AC: 79067 AN: 151948 Hom.: 22340 Cov.: 31 AF XY: 0.519 AC XY: 38548 AN XY: 74274

African (AFR) AF: 0.733 AC: 30388 AN: 41432

American (AMR) AF: 0.419 AC: 6402 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3468

East Asian (EAS) AF: 0.757 AC: 3900 AN: 5154

South Asian (SAS) AF: 0.539 AC: 2592 AN: 4808

European-Finnish (FIN) AF: 0.388 AC: 4102 AN: 10560

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28461 AN: 67946

Other (OTH) AF: 0.524 AC: 1107 AN: 2114

Alfa AF: 0.467 Hom.: 2936

Bravo AF: 0.532

TwinsUK AF: 0.410 AC: 1521

ALSPAC AF: 0.403 AC: 1553

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.95	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.29
DANN	Benign	0.74
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0034	T
PhyloP100		-1.2
Sift4G	Benign	0.22	T
Vest4		0.10
MVP		0.13
GERP RS		-4.7
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: rs7763880; hg19: chr6-152802297;