rs583362

Positions:

• chr11-107707995-C-G

Variant summary

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

The NM_003063.3(SLN):​c.-65G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,067,646 control chromosomes in the GnomAD database, including 180,634 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 0.60 (28174 hom., cov: 31)
  • Exomes 𝑓: 0.58 (152460 hom.)
• Consequence: SLN NM_003063.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843

Genes affected

SLN (HGNC:11089): (sarcolipin) Sarcoplasmic reticulum Ca(2+)-ATPases are transmembrane proteins that catalyze the ATP-dependent transport of Ca(2+) from the cytosol into the lumen of the sarcoplasmic reticulum in muscle cells. This gene encodes a small proteolipid that regulates several sarcoplasmic reticulum Ca(2+)-ATPases. The transmembrane protein interacts with Ca(2+)-ATPases and reduces the accumulation of Ca(2+) in the sarcoplasmic reticulum without affecting the rate of ATP hydrolysis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLN	NM_003063.3	c.-65G>C		5_prime_UTR_variant	2/2	ENST00000305991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLN	ENST00000305991.3	c.-65G>C		5_prime_UTR_variant	2/2	1	NM_003063.3	P1
SLN	ENST00000525934.1	c.-65G>C		5_prime_UTR_variant	2/2	3		P1
SLN	ENST00000531293.1	c.-65G>C		5_prime_UTR_variant	3/3	4		P1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91548 AN: 151832 Hom.: 28136 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.576 AC: 527292 AN: 915696 Hom.: 152460 Cov.: 12 AF XY: 0.570 AC XY: 272891 AN XY: 479016

Gnomad4 AFR exome AF: 0.697

Gnomad4 AMR exome AF: 0.666

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.603 AC: 91641 AN: 151950 Hom.: 28174 Cov.: 31 AF XY: 0.610 AC XY: 45269 AN XY: 74252

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.602

Alfa AF: 0.565 Hom.: 3090

Bravo AF: 0.613

Asia WGS AF: 0.686 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.8
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs583362; hg19: chr11-107578721; COSMIC: COSV60007139;