rs772000149

Variant names:

• chr6-152347130-T-A
• NM_182961.4:c.12007A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152347130-T-A
• chr6-152347130-T-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_182961.4(SYNE1):​c.12007A>T​(p.Lys4003*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYNE1 NM_182961.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.47

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• 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.12007A>T	p.Lys4003*	stop_gained	Exon 73 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.12007A>T	p.Lys4003*	stop_gained	Exon 73 of 146	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.11794A>T	p.Lys3932*	stop_gained	Exon 72 of 146	1		ENSP00000396024.1
SYNE1	ENST00000471834.1	n.5145A>T		non_coding_transcript_exon_variant	Exon 16 of 19	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
Vest4		0.92
GERP RS		5.9

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-152668265;