6-152176365-C-T

Variant names:

• chr6-152176365-C-T
• rs41292868
• NM_182961.4:c.23627+29G>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.23627+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,613,256 control chromosomes in the GnomAD database, including 2,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (155 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2486 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.35
• Publications: 4 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=-0.87).
• BP6: Variant 6-152176365-C-T is Benign according to our data. Variant chr6-152176365-C-T is described in ClinVar as Benign. ClinVar VariationId is 262187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.23627+29G>A		intron_variant	Intron 130 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.23627+29G>A		intron_variant	Intron 130 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6039 AN: 152138 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0346

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0497

GnomAD2 exomes AF: 0.0411 AC: 10328 AN: 251344 AF XY: 0.0421

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.0343

Gnomad ASJ exome AF: 0.0431

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.0344

Gnomad NFE exome AF: 0.0619

Gnomad OTH exome AF: 0.0556

GnomAD4 exome AF: 0.0541 AC: 79105 AN: 1461000 Hom.: 2486 Cov.: 31 AF XY: 0.0530 AC XY: 38516 AN XY: 726854

African (AFR) AF: 0.0107 AC: 359 AN: 33460

American (AMR) AF: 0.0356 AC: 1592 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0394 AC: 1029 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39688

South Asian (SAS) AF: 0.0141 AC: 1217 AN: 86234

European-Finnish (FIN) AF: 0.0353 AC: 1886 AN: 53412

Middle Eastern (MID) AF: 0.0817 AC: 446 AN: 5462

European-Non Finnish (NFE) AF: 0.0626 AC: 69575 AN: 1111564

Other (OTH) AF: 0.0497 AC: 2996 AN: 60332

GnomAD4 genome AF: 0.0396 AC: 6036 AN: 152256 Hom.: 155 Cov.: 32 AF XY: 0.0383 AC XY: 2851 AN XY: 74430

African (AFR) AF: 0.0118 AC: 492 AN: 41562

American (AMR) AF: 0.0357 AC: 546 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4826

European-Finnish (FIN) AF: 0.0346 AC: 367 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0621 AC: 4221 AN: 68012

Other (OTH) AF: 0.0496 AC: 105 AN: 2116

Alfa AF: 0.0404 Hom.: 52

Bravo AF: 0.0398

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 28, 2018

GeneDx

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	-0.87
CADD	Benign	0.027
DANN	Benign	0.72
PhyloP100		-3.3
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: rs41292868; hg19: chr6-152497500;