12-26186798-C-T

Position:

• chr12-26186798-C-T

Variant summary

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

The ENST00000540266.5(SSPN):​c.-30-37495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,078 control chromosomes in the GnomAD database, including 6,168 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 0.28 (6168 hom., cov: 32)
• Consequence: SSPN ENST00000540266.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSPN	XM_011520853.4	c.-30-37495C>T		intron_variant			XP_011519155.1
SSPN	XM_011520855.2	c.-30-37495C>T		intron_variant			XP_011519157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSPN	ENST00000538142.5	c.-30-37495C>T		intron_variant		4		ENSP00000445360
SSPN	ENST00000540266.5	c.-30-37495C>T		intron_variant		4		ENSP00000442893
SSPN	ENST00000534829.5	n.101+64646C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43014 AN: 151960 Hom.: 6166 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.283 AC: 43038 AN: 152078 Hom.: 6168 Cov.: 32 AF XY: 0.285 AC XY: 21214 AN XY: 74324

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.248

Alfa AF: 0.267 Hom.: 1012

Bravo AF: 0.273

Asia WGS AF: 0.344 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7955859; hg19: chr12-26339731;