chr6-152380861-C-T

Position:

• chr6-152380861-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182961.4(SYNE1):​c.9009+145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 776,354 control chromosomes in the GnomAD database, including 69,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11565 hom., cov: 33)
  • Exomes 𝑓: 0.43 (58298 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.332

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-AS1 (HGNC:40793): (SYNE1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 6-152380861-C-T is Benign according to our data. Variant chr6-152380861-C-T is described in ClinVar as [Benign]. Clinvar id is 1265597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.9009+145G>A		intron_variant		ENST00000367255.10	NP_892006.3
SYNE1-AS1	NR_120501.1	n.65-199C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.9009+145G>A		intron_variant		1	NM_182961.4	ENSP00000356224	P1
SYNE1-AS1	ENST00000412161.1	n.49-199C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57252 AN: 151976 Hom.: 11572 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.426 AC: 266130 AN: 624260 Hom.: 58298 AF XY: 0.428 AC XY: 142528 AN XY: 332956

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.445

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.376 AC: 57259 AN: 152094 Hom.: 11565 Cov.: 33 AF XY: 0.379 AC XY: 28158 AN XY: 74344

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.375

Alfa AF: 0.407 Hom.: 4294

Bravo AF: 0.358

Asia WGS AF: 0.287 AC: 996 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.2
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs214958; hg19: chr6-152701996;