6-152148739-T-C

Position:

• chr6-152148739-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182961.4(SYNE1):​c.24643-361A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,440 control chromosomes in the GnomAD database, including 5,588 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 0.26 (5588 hom., cov: 30)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.24643-361A>G		intron_variant		ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2	c.1108-361A>G		intron_variant		ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.24643-361A>G		intron_variant		1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5	c.1108-361A>G		intron_variant		5	NM_001347702.2	ENSP00000346701.4

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39663 AN: 151330 Hom.: 5583 Cov.: 30

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39689 AN: 151440 Hom.: 5588 Cov.: 30 AF XY: 0.264 AC XY: 19523 AN XY: 74010

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.286

Alfa AF: 0.289 Hom.: 1839

Bravo AF: 0.275

Asia WGS AF: 0.331 AC: 1149 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.72
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs718528; hg19: chr6-152469874; COSMIC: COSV55000788; COSMIC: COSV55000788;