rs143118084

Variant names:

• chr6-152239673-A-C
• rs143118084
• NM_182961.4:c.19927T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-152239673-A-C
• chr6-152239673-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182961.4(SYNE1):​c.19927T>G​(p.Leu6643Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L6643L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYNE1 NM_182961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.19927T>G	p.Leu6643Val	missense_variant	Exon 108 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.19927T>G	p.Leu6643Val	missense_variant	Exon 108 of 146	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.19714T>G	p.Leu6572Val	missense_variant	Exon 107 of 146	1		ENSP00000396024.1
SYNE1	ENST00000367256.9	n.3619T>G		non_coding_transcript_exon_variant	Exon 23 of 61	1
SYNE1	ENST00000409694.6	n.3511T>G		non_coding_transcript_exon_variant	Exon 21 of 59	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.8	M;.;.
PhyloP100		1.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.5	D;N;D
REVEL	Uncertain	0.30
Sift	Benign	0.060	T;T;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.68
MutPred		0.38		Gain of catalytic residue at L6643 (P = 0.0746);.;.;
MVP		0.63
MPC		0.20
ClinPred		0.97	D
GERP RS		0.83
Varity_R		0.19
gMVP		0.25
Mutation Taster		=88/12	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs143118084; hg19: chr6-152560808;