NM_182961.4:c.*103C>A

Variant names:

Variant summary

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

The NM_182961.4(SYNE1):c.*103C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,594,380 control chromosomes in the GnomAD database, including 45,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3613 hom., cov: 33)

Exomes 𝑓: 0.24 ( 42147 hom. )

Consequence

SYNE1
NM_182961.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0230

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:

ESR1 (HGNC:3467): (estrogen receptor 1) This gene encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by this gene plays a key role in breast cancer, endometrial cancer, and osteoporosis. This gene is reported to have dozens of transcript variants due to the use of alternate promoters and alternative splicing, however, the full-length nature of many of these variants remain uncertain. [provided by RefSeq, Jul 2020]

ESR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-152122333-G-T is Benign according to our data. Variant chr6-152122333-G-T is described in ClinVar as [Benign]. Clinvar id is 355804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.*103C>A		3_prime_UTR_variant	Exon 146 of 146	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2 link	c.*103C>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255 link	c.*103C>A		3_prime_UTR_variant	Exon 146 of 146	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1
SYNE1	ENST00000354674 link	c.*103C>A		3_prime_UTR_variant	Exon 18 of 18	5	NM_001347702.2	ENSP00000346701.4		F8WAI0

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31446

AN:

152110

Hom.:

3615

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.232

GnomAD4 exome

AF:

0.237

AC:

342397

AN:

1442152

Hom.:

42147

Cov.:

AF XY:

0.241

AC XY:

172753

AN XY:

717658

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.316

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.303

Gnomad4 SAS exome

AF:

0.344

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.232

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.207

AC:

31461

AN:

152228

Hom.:

3613

Cov.:

AF XY:

0.208

AC XY:

15518

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.233

Hom.:

4204

Bravo

AF:

0.214

Asia WGS

AF:

0.308

AC:

1067

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

DANN

Benign

0.63

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