Variant 6-152399844-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.7030-21T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00989 in 1,607,480 control chromosomes in the GnomAD database, including 1,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.051 ( 631 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 598 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.520

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-152399844-A-T is Benign according to our data. Variant chr6-152399844-A-T is described in ClinVar as [Benign]. Clinvar id is 262199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.7030-21T>A		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.7030-21T>A	intron_variant	1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.7051-21T>A	intron_variant	1		ENSP00000396024
SYNE1	ENST00000461872.6 linkuse as main transcript	n.7248-21T>A	intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0509

AC:

7742

AN:

152134

Hom.:

629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0136

AC:

3407

AN:

250620

Hom.:

289

AF XY:

0.00983

AC XY:

1332

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.181

Gnomad AMR exome

AF:

0.00939

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000848

Gnomad OTH exome

AF:

0.00606

GnomAD4 exome

AF:

0.00559

AC:

8131

AN:

1455228

Hom.:

598

Cov.:

AF XY:

0.00492

AC XY:

3565

AN XY:

724322

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.0114

Gnomad4 ASJ exome

AF:

0.000652

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000360

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000664

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0511

AC:

7773

AN:

152252

Hom.:

631

Cov.:

AF XY:

0.0499

AC XY:

3713

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.0220

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.00392

Hom.:

Bravo

AF:

0.0593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.18

DANN

Benign

0.70

BranchPoint Hunter

1.0

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over