rs139384691

Variant names:

• chr6-152236833-C-A
• rs139384691
• NM_182961.4:c.20183G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152236833-C-A
• chr6-152236833-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182961.4(SYNE1):​c.20183G>T​(p.Arg6728Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNE1 NM_182961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.20183G>T	p.Arg6728Leu	missense_variant	Exon 109 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.20183G>T	p.Arg6728Leu	missense_variant	Exon 109 of 146	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.19970G>T	p.Arg6657Leu	missense_variant	Exon 108 of 146	1		ENSP00000396024.1
SYNE1	ENST00000367256.9	n.3875G>T		non_coding_transcript_exon_variant	Exon 24 of 61	1
SYNE1	ENST00000409694.6	n.3767G>T		non_coding_transcript_exon_variant	Exon 22 of 59	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.5	D;.;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.87
MutPred		0.36		Loss of disorder (P = 0.0953);.;.;
MVP		0.52
MPC		0.66
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.59
gMVP		0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139384691; hg19: chr6-152557968;