12-26210970-A-C

Position:

• chr12-26210970-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005086.5(SSPN):​c.280-13323A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,008 control chromosomes in the GnomAD database, including 5,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5486 hom., cov: 32)
• Consequence: SSPN NM_005086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

Genes affected

SSPN (HGNC:11322): (sarcospan) This gene encodes a member of the dystrophin-glycoprotein complex (DGC). The DGC spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Two alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSPN	NM_005086.5	c.280-13323A>C		intron_variant		ENST00000242729.7
SSPN	NM_001135823.1	c.-30-13323A>C		intron_variant
SSPN	XM_011520853.4	c.-30-13323A>C		intron_variant
SSPN	XM_011520855.2	c.-30-13323A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSPN	ENST00000242729.7	c.280-13323A>C		intron_variant		1	NM_005086.5	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39328 AN: 151890 Hom.: 5478 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39359 AN: 152008 Hom.: 5486 Cov.: 32 AF XY: 0.267 AC XY: 19802 AN XY: 74298

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.266

Alfa AF: 0.247 Hom.: 8087

Bravo AF: 0.249

Asia WGS AF: 0.491 AC: 1702 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs2291138; hg19: chr12-26363903;