rs79486252

Variant names:

• chr6-152354758-T-A
• NM_182961.4:c.10827A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152354758-T-A
• chr6-152354758-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182961.4(SYNE1):​c.10827A>T​(p.Gln3609His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in Lovd.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYNE1 NM_182961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110713184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.10827A>T	p.Gln3609His	missense_variant	Exon 67 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.10827A>T	p.Gln3609His	missense_variant	Exon 67 of 146	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.10848A>T	p.Gln3616His	missense_variant	Exon 67 of 146	1		ENSP00000396024.1
SYNE1	ENST00000471834.1	n.3965A>T		non_coding_transcript_exon_variant	Exon 10 of 19	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727248

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.26	T;.;T
Eigen	Benign	-0.088
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N;D;N
REVEL	Benign	0.048
Sift	Benign	0.040	D;D;D
Sift4G	Benign	0.10	T;T;T
Polyphen		0.91	P;.;.
Vest4		0.11
MutPred		0.30		Loss of disorder (P = 0.073);.;.;
MVP		0.39
MPC		0.24
ClinPred		0.35	T
GERP RS		0.26
Varity_R		0.085
gMVP		0.21

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: chr6-152675893;