rs778218574

Variant names:

• chr11-66691327-C-G
• NM_006946.4:c.5522G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-66691327-C-G
• chr11-66691327-C-T

Variant summary

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

The NM_006946.4(SPTBN2):​c.5522G>C​(p.Arg1841Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,401,132 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPTBN2 NM_006946.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

Genes affected

SPTBN2 (HGNC:11276): (spectrin beta, non-erythrocytic 2) Spectrins are principle components of a cell's membrane-cytoskeleton and are composed of two alpha and two beta spectrin subunits. The protein encoded by this gene (SPTBN2), is called spectrin beta non-erythrocytic 2 or beta-III spectrin. It is related to, but distinct from, the beta-II spectrin gene which is also known as spectrin beta non-erythrocytic 1 (SPTBN1). SPTBN2 regulates the glutamate signaling pathway by stabilizing the glutamate transporter EAAT4 at the surface of the plasma membrane. Mutations in this gene cause a form of spinocerebellar ataxia, SCA5, that is characterized by neurodegeneration, progressive locomotor incoordination, dysarthria, and uncoordinated eye movements. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
SPTBN2	NM_006946.4	c.5522G>C	p.Arg1841Pro	missense_variant	Exon 27 of 38	ENST00000533211.6	NP_008877.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN2	ENST00000533211.6	c.5522G>C	p.Arg1841Pro	missense_variant	Exon 27 of 38	5	NM_006946.4	ENSP00000432568.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1401132 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 688158

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: 0.00000186

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	Pathogenic	0.76
BayesDel_addAF	Benign	0.0098	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;.
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.2	L;L;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.089	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.83	P;P;.
Vest4		0.57
MutPred		0.68		Loss of stability (P = 0.1363);Loss of stability (P = 0.1363);Loss of stability (P = 0.1363);
MVP		0.51
MPC		1.3
ClinPred		0.80	D
GERP RS		3.8
Varity_R		0.60
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr11-66458798;