chr12-26230878-C-T

Variant names:

• chr12-26230878-C-T
• rs117506538
• NM_005086.5:c.534C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005086.5(SSPN):​c.534C>T​(p.Tyr178Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,172 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (105 hom.)
• Consequence: SSPN NM_005086.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.11
• Publications: 4 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]

ENSG00000255750 (HGNC:):

SSPN-AS1 (HGNC:56072): (ITPR2 and SSPN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 12-26230878-C-T is Benign according to our data. Variant chr12-26230878-C-T is described in ClinVar as Benign. ClinVar VariationId is 782779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005086.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSPN	NM_005086.5	MANE Select	c.534C>T	p.Tyr178Tyr	synonymous	Exon 3 of 3	NP_005077.2
	SSPN	NM_001135823.1		c.225C>T	p.Tyr75Tyr	synonymous	Exon 3 of 3	NP_001129295.1	Q14714-3
	SSPN-AS1	NR_187464.1		n.470G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSPN	ENST00000242729.7	TSL:1 MANE Select	c.534C>T	p.Tyr178Tyr	synonymous	Exon 3 of 3	ENSP00000242729.2	Q14714-1
	SSPN	ENST00000535504.1	TSL:1	c.366+6499C>T		intron	N/A	ENSP00000438801.1	F5H0K2
	SSPN	ENST00000858023.1		c.447C>T	p.Tyr149Tyr	synonymous	Exon 2 of 2	ENSP00000528082.1

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 511 AN: 152188 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00721 AC: 1813 AN: 251464 AF XY: 0.00639

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0934

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00191 AC: 2798 AN: 1461866 Hom.: 105 Cov.: 31 AF XY: 0.00179 AC XY: 1300 AN XY: 727238

African (AFR) AF: 0.000508 AC: 17 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0582 AC: 2310 AN: 39700

South Asian (SAS) AF: 0.00146 AC: 126 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1112010

Other (OTH) AF: 0.00467 AC: 282 AN: 60396

GnomAD4 genome AF: 0.00334 AC: 508 AN: 152306 Hom.: 13 Cov.: 33 AF XY: 0.00418 AC XY: 311 AN XY: 74472

African (AFR) AF: 0.000987 AC: 41 AN: 41554

American (AMR) AF: 0.000849 AC: 13 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0816 AC: 423 AN: 5184

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68038

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.000398 Hom.: 1

Bravo AF: 0.00382

Asia WGS AF: 0.0280 AC: 98 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs117506538; hg19: chr12-26383811; COSMIC: COSV54382057; COSMIC: COSV54382057;