12-26157174-G-A

Variant names:

• chr12-26157174-G-A
• rs1993973
• ENST00000539019.1:n.67+22144G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000539019.1(SSPN):​n.67+22144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,074 control chromosomes in the GnomAD database, including 52,816 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 0.80 (52816 hom., cov: 31)
• Consequence: SSPN ENST00000539019.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 3 publications found

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]

ENSG00000286752 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539019.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSPN	ENST00000539019.1	TSL:1	n.67+22144G>A		intron	N/A
	SSPN	ENST00000540266.5	TSL:4	c.-31+22144G>A		intron	N/A	ENSP00000442893.1
	SSPN	ENST00000538142.5	TSL:4	c.-31+35022G>A		intron	N/A	ENSP00000445360.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121102 AN: 151956 Hom.: 52815 Cov.: 31

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.796 AC: 121126 AN: 152074 Hom.: 52816 Cov.: 31 AF XY: 0.800 AC XY: 59518 AN XY: 74366

African (AFR) AF: 0.407 AC: 16852 AN: 41370

American (AMR) AF: 0.873 AC: 13337 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3335 AN: 3472

East Asian (EAS) AF: 0.940 AC: 4860 AN: 5168

South Asian (SAS) AF: 0.845 AC: 4076 AN: 4824

European-Finnish (FIN) AF: 0.985 AC: 10463 AN: 10620

Middle Eastern (MID) AF: 0.842 AC: 246 AN: 292

European-Non Finnish (NFE) AF: 0.960 AC: 65310 AN: 68024

Other (OTH) AF: 0.832 AC: 1756 AN: 2110

Alfa AF: 0.882 Hom.: 17499

Bravo AF: 0.772

Asia WGS AF: 0.859 AC: 2986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.75
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1993973; hg19: chr12-26310107;