chr6-152481162-T-C

Position:

• chr6-152481162-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.1350+1923A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 206,248 control chromosomes in the GnomAD database, including 27,940 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 0.52 (22340 hom., cov: 31)
  • Exomes 𝑓: 0.43 (5600 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 (MetaRNN=0.0034042597).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.1350+1923A>G		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.1350+1923A>G		intron_variant		1	NM_182961.4	ENSP00000356224	P1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78973 AN: 151830 Hom.: 22295 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.426 AC: 23119 AN: 54300 Hom.: 5600 Cov.: 0 AF XY: 0.432 AC XY: 12456 AN XY: 28854

Gnomad4 AFR exome AF: 0.717

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.465

Gnomad4 EAS exome AF: 0.770

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.520 AC: 79067 AN: 151948 Hom.: 22340 Cov.: 31 AF XY: 0.519 AC XY: 38548 AN XY: 74274

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.524

Alfa AF: 0.467 Hom.: 2936

Bravo AF: 0.532

TwinsUK AF: 0.410 AC: 1521

ALSPAC AF: 0.403 AC: 1553

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.95	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.29
DANN	Benign	0.74
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0034	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P
Sift4G	Benign	0.22	T
Vest4		0.10
MVP		0.13
GERP RS		-4.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7763880; hg19: chr6-152802297;