NM_003063.3:c.-65G>C

Variant names:

• chr11-107707995-C-G
• rs583362
• NM_003063.3:c.-65G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003063.3. 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
	SLN	NM_003063.3	MANE Select	c.-65G>C		5_prime_UTR	Exon 2 of 2	NP_003054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLN	ENST00000305991.3	TSL:1 MANE Select	c.-65G>C		5_prime_UTR	Exon 2 of 2	ENSP00000304707.2
	SLN	ENST00000525934.1	TSL:3	c.-65G>C		5_prime_UTR	Exon 2 of 2	ENSP00000434189.1
	SLN	ENST00000531293.1	TSL:4	c.-65G>C		5_prime_UTR	Exon 3 of 3	ENSP00000435380.1

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

African (AFR) AF: 0.697 AC: 16208 AN: 23266

American (AMR) AF: 0.666 AC: 29106 AN: 43716

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 11808 AN: 22598

East Asian (EAS) AF: 0.874 AC: 32667 AN: 37370

South Asian (SAS) AF: 0.502 AC: 37613 AN: 74934

European-Finnish (FIN) AF: 0.579 AC: 30751 AN: 53094

Middle Eastern (MID) AF: 0.550 AC: 2594 AN: 4718

European-Non Finnish (NFE) AF: 0.558 AC: 342261 AN: 613486

Other (OTH) AF: 0.571 AC: 24284 AN: 42514

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

African (AFR) AF: 0.683 AC: 28282 AN: 41436

American (AMR) AF: 0.644 AC: 9837 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3468

East Asian (EAS) AF: 0.842 AC: 4325 AN: 5138

South Asian (SAS) AF: 0.509 AC: 2453 AN: 4816

European-Finnish (FIN) AF: 0.596 AC: 6278 AN: 10532

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36753 AN: 67968

Other (OTH) AF: 0.602 AC: 1272 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.8
DANN	Benign	0.84
PhyloP100		0.84
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs583362; hg19: chr11-107578721; COSMIC: COSV60007139;