rs2292307

chr10-73790158-C-Achr10-73790158-C-Gchr10-73790158-C-T

Variant summary

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

The NM_001367799.1(ZSWIM8):c.821-14C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,610,122 control chromosomes in the GnomAD database, including 15,552 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 0.12 (1149 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14403 hom.)
• Consequence: ZSWIM8 NM_001367799.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

Genes affected

ZSWIM8 (HGNC:23528): (zinc finger SWIM-type containing 8) Enables ubiquitin ligase-substrate adaptor activity. Involved in positive regulation of miRNA catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSWIM8	NM_001367799.1	c.821-14C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000604729.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSWIM8	ENST00000604729.6	c.821-14C>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001367799.1	A1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17736 AN: 152082 Hom.: 1148 Cov.: 32

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.140 AC: 34248 AN: 245366 Hom.: 2613 AF XY: 0.146 AC XY: 19433 AN XY: 132976

Gnomad AFR exome AF: 0.0752

Gnomad AMR exome AF: 0.0896

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.216

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.137 AC: 199491 AN: 1457922 Hom.: 14403 Cov.: 34 AF XY: 0.140 AC XY: 101503 AN XY: 724952

Gnomad4 AFR exome AF: 0.0696

Gnomad4 AMR exome AF: 0.0883

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.117 AC: 17742 AN: 152200 Hom.: 1149 Cov.: 32 AF XY: 0.116 AC XY: 8665 AN XY: 74418

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.0948

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.113

Alfa AF: 0.132 Hom.: 2058

Bravo AF: 0.113

Asia WGS AF: 0.136 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	19
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2292307; hg19: chr10-75549916; COSMIC: COSV67131693; COSMIC: COSV67131693;