rs139671151

Variant names:

• chr6-152141345-C-A
• rs139671151
• NM_182961.4:c.25120-16G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152141345-C-A
• chr6-152141345-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_182961.4(SYNE1):​c.25120-16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0068 in 1,613,292 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (83 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0330
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive ataxia, Beauce type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive myogenic arthrogryposis multiplex congenita

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000300811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-152141345-C-A is Benign according to our data. Variant chr6-152141345-C-A is described in ClinVar as Benign. ClinVar VariationId is 262192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00668 (1017/152278) while in subpopulation AMR AF = 0.0169 (259/15298). AF 95% confidence interval is 0.0152. There are 5 homozygotes in GnomAd4. There are 521 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.25120-16G>T		intron_variant	Intron 138 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2	c.1654-16G>T		intron_variant	Intron 10 of 17	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.25120-16G>T		intron_variant	Intron 138 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5	c.1654-16G>T		intron_variant	Intron 10 of 17	5	NM_001347702.2	ENSP00000346701.4

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 1016 AN: 152160 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00768

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00719

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00822 AC: 2067 AN: 251400 AF XY: 0.00851

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.00954

Gnomad ASJ exome AF: 0.0249

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00918

Gnomad OTH exome AF: 0.0137

GnomAD4 exome AF: 0.00682 AC: 9957 AN: 1461014 Hom.: 83 Cov.: 32 AF XY: 0.00711 AC XY: 5166 AN XY: 726834

African (AFR) AF: 0.00176 AC: 59 AN: 33454

American (AMR) AF: 0.00984 AC: 440 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0226 AC: 591 AN: 26124

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39682

South Asian (SAS) AF: 0.00962 AC: 830 AN: 86236

European-Finnish (FIN) AF: 0.00167 AC: 89 AN: 53258

Middle Eastern (MID) AF: 0.0289 AC: 157 AN: 5438

European-Non Finnish (NFE) AF: 0.00650 AC: 7230 AN: 1111800

Other (OTH) AF: 0.00923 AC: 557 AN: 60328

GnomAD4 genome AF: 0.00668 AC: 1017 AN: 152278 Hom.: 5 Cov.: 32 AF XY: 0.00700 AC XY: 521 AN XY: 74456

African (AFR) AF: 0.00190 AC: 79 AN: 41552

American (AMR) AF: 0.0169 AC: 259 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00789 AC: 38 AN: 4814

European-Finnish (FIN) AF: 0.000849 AC: 9 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00719 AC: 489 AN: 68032

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.00917 Hom.: 4

Bravo AF: 0.00813

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 06, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SYNE1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		0.033
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs139671151; hg19: chr6-152462480;