rs1481121106

Variant names:

• chr6-152419600-A-C
• NM_182961.4:c.5390T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-152419600-A-C
• chr6-152419600-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_182961.4(SYNE1):​c.5390T>G​(p.Met1797Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. M1797T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: SYNE1 NM_182961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053511262).
• BS2: High AC in GnomAdExome4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.5390T>G	p.Met1797Arg	missense_variant	Exon 40 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.5390T>G	p.Met1797Arg	missense_variant	Exon 40 of 146	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.5411T>G	p.Met1804Arg	missense_variant	Exon 40 of 146	1		ENSP00000396024.1
SYNE1	ENST00000461872.6	n.5608T>G		non_coding_transcript_exon_variant	Exon 38 of 55	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1461748 Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14 AN XY: 727164

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: 0.0000243

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.0040
DANN	Benign	0.49
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.97	N;.;N
REVEL	Benign	0.068
Sift	Benign	0.15	T;.;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.092
MutPred		0.28		Loss of stability (P = 0.0481);.;.;
MVP		0.13
MPC		0.20
ClinPred		0.13	T
GERP RS		-8.5
Varity_R		0.16
gMVP		0.15

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: chr6-152740735;