rs13975

Positions:

• chr3-125083387-T-C

Variant summary

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

The NM_024628.6(SLC12A8):​c.*503A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 157,016 control chromosomes in the GnomAD database, including 30,100 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 0.61 (29387 hom., cov: 29)
  • Exomes 𝑓: 0.51 (713 hom.)
• Consequence: SLC12A8 NM_024628.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

Genes affected

SLC12A8 (HGNC:15595): (solute carrier family 12 member 8) This gene is thought to be a candidate for psoriasis susceptibility. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A8	NM_024628.6	c.*503A>G		3_prime_UTR_variant	14/14	ENST00000469902.6	NP_078904.4
SLC12A8	NM_001195483.2	c.*503A>G		3_prime_UTR_variant	13/13		NP_001182412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A8	ENST00000469902.6	c.*503A>G		3_prime_UTR_variant	14/14	2	NM_024628.6	ENSP00000418783	P1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92591 AN: 151690 Hom.: 29336 Cov.: 29

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.563

GnomAD4 exome AF: 0.507 AC: 2635 AN: 5202 Hom.: 713 Cov.: 0 AF XY: 0.501 AC XY: 1378 AN XY: 2752

Gnomad4 AFR exome AF: 0.867

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.550

Gnomad4 EAS exome AF: 0.622

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.611 AC: 92709 AN: 151814 Hom.: 29387 Cov.: 29 AF XY: 0.613 AC XY: 45518 AN XY: 74202

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.561

Alfa AF: 0.529 Hom.: 31820

Bravo AF: 0.618

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.3
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs13975; hg19: chr3-124802231;