ENST00000539019.1:n.67+22144G>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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSPN	XM_011520853.4	c.-31+35022G>A		intron_variant	Intron 1 of 2		XP_011519155.1
SSPN	XM_011520855.2	c.-31+22144G>A		intron_variant	Intron 1 of 2		XP_011519157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSPN	ENST00000539019.1	n.67+22144G>A		intron_variant	Intron 1 of 1	1
SSPN	ENST00000540266.5	c.-31+22144G>A		intron_variant	Intron 1 of 2	4		ENSP00000442893.1
SSPN	ENST00000538142.5	c.-31+35022G>A		intron_variant	Intron 1 of 2	4		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 v4.3

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;