6-152236976-TA-TAA

Variant names:

• chr6-152236976-T-TA
• rs36215566
• NM_182961.4:c.20068-29dupT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.20068-29dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,611,122 control chromosomes in the GnomAD database, including 39,899 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3550 hom., cov: 28)
  • Exomes 𝑓: 0.22 (36349 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.407

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-152236976-T-TA is Benign according to our data. Variant chr6-152236976-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 262177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.20068-29dupT		intron_variant	Intron 108 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.20068-29_20068-28insT		intron_variant	Intron 108 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.19855-29_19855-28insT		intron_variant	Intron 107 of 145	1		ENSP00000396024.1
SYNE1	ENST00000367256.9	n.3760-29_3760-28insT		intron_variant	Intron 23 of 60	1
SYNE1	ENST00000409694.6	n.3652-29_3652-28insT		intron_variant	Intron 21 of 58	1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29807 AN: 151958 Hom.: 3542 Cov.: 28

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.243 AC: 59990 AN: 246790 Hom.: 8327 AF XY: 0.237 AC XY: 31530 AN XY: 133316

Gnomad AFR exome AF: 0.0769

Gnomad AMR exome AF: 0.451

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.220

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.217 AC: 317291 AN: 1459046 Hom.: 36349 Cov.: 32 AF XY: 0.217 AC XY: 157444 AN XY: 725758

Gnomad4 AFR exome AF: 0.0764

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.196 AC: 29839 AN: 152076 Hom.: 3550 Cov.: 28 AF XY: 0.202 AC XY: 15030 AN XY: 74328

Gnomad4 AFR AF: 0.0792

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.214

Alfa AF: 0.151 Hom.: 437

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Significance: Benign/Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs36215566; hg19: chr6-152558111;