6-152309811-C-T

Variant names:

• chr6-152309811-C-T
• rs12662994
• NM_182961.4:c.17202+24G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.17202+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,612,526 control chromosomes in the GnomAD database, including 10,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (1032 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9323 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.03
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-152309811-C-T is Benign according to our data. Variant chr6-152309811-C-T is described in ClinVar as Benign. ClinVar VariationId is 262171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.17202+24G>A		intron_variant	Intron 90 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.17202+24G>A		intron_variant	Intron 90 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14857 AN: 152130 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.132 AC: 33061 AN: 250328 AF XY: 0.127

Gnomad AFR exome AF: 0.0449

Gnomad AMR exome AF: 0.331

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.0894

Gnomad FIN exome AF: 0.0782

Gnomad NFE exome AF: 0.0957

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.101 AC: 147696 AN: 1460276 Hom.: 9323 Cov.: 31 AF XY: 0.102 AC XY: 73965 AN XY: 726538

African (AFR) AF: 0.0444 AC: 1487 AN: 33462

American (AMR) AF: 0.322 AC: 14397 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4070 AN: 26126

East Asian (EAS) AF: 0.116 AC: 4601 AN: 39698

South Asian (SAS) AF: 0.145 AC: 12534 AN: 86180

European-Finnish (FIN) AF: 0.0796 AC: 4178 AN: 52478

Middle Eastern (MID) AF: 0.145 AC: 793 AN: 5470

European-Non Finnish (NFE) AF: 0.0892 AC: 99160 AN: 1111818

Other (OTH) AF: 0.107 AC: 6476 AN: 60352

GnomAD4 genome AF: 0.0976 AC: 14861 AN: 152250 Hom.: 1032 Cov.: 32 AF XY: 0.101 AC XY: 7538 AN XY: 74426

African (AFR) AF: 0.0472 AC: 1961 AN: 41568

American (AMR) AF: 0.239 AC: 3657 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3472

East Asian (EAS) AF: 0.101 AC: 523 AN: 5178

South Asian (SAS) AF: 0.134 AC: 647 AN: 4816

European-Finnish (FIN) AF: 0.0856 AC: 908 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6304 AN: 68016

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.108 Hom.: 928

Bravo AF: 0.109

Asia WGS AF: 0.132 AC: 457 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 28, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arthrogryposis multiplex congenita 3, myogenic type Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.57
PhyloP100		-1.0
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: rs12662994; hg19: chr6-152630946; COSMIC: COSV54995521;