rs200276242

Variant names:

• chr6-152442149-C-G
• rs200276242
• NM_182961.4:c.3934G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-152442149-C-G
• chr6-152442149-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_182961.4(SYNE1):​c.3934G>C​(p.Glu1312Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1312D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SYNE1 NM_182961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 10 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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2823568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.3934G>C	p.Glu1312Gln	missense_variant	Exon 31 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.3934G>C	p.Glu1312Gln	missense_variant	Exon 31 of 146	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461586 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;T;.;.;.
Eigen	Benign	-0.0055
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	T;T;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	1.4	L;.;.;L;.;L
PhyloP100		1.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.65	N;.;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.24	T;.;T;T;T;T
Sift4G	Benign	0.24	T;T;T;T;T;T
Polyphen		0.40	B;.;.;P;P;.
Vest4		0.32
MutPred		0.23		Gain of MoRF binding (P = 0.0563);.;.;Gain of MoRF binding (P = 0.0563);.;Gain of MoRF binding (P = 0.0563);
MVP		0.83
MPC		0.30
ClinPred		0.69	D
GERP RS		5.2
Varity_R		0.088
gMVP		0.12
Mutation Taster		=85/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs200276242; hg19: chr6-152763284;