rs2292307

Variant names:

• chr10-73790158-C-A
• rs2292307
• NM_001367799.1:c.821-14C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-73790158-C-A
• chr10-73790158-C-G
• chr10-73790158-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367799.1(ZSWIM8):​c.821-14C>A variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZSWIM8	NM_001367799.1	c.821-14C>A		intron_variant	Intron 6 of 25	ENST00000604729.6	NP_001354728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM8	ENST00000604729.6	c.821-14C>A		intron_variant	Intron 6 of 25	5	NM_001367799.1	ENSP00000474944.1

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

GnomAD2 exomes AF: 0.140 AC: 34248 AN: 245366 AF XY: 0.146

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 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

African (AFR) AF: 0.0696 AC: 2327 AN: 33424

American (AMR) AF: 0.0883 AC: 3922 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5794 AN: 25824

East Asian (EAS) AF: 0.124 AC: 4906 AN: 39672

South Asian (SAS) AF: 0.216 AC: 18471 AN: 85692

European-Finnish (FIN) AF: 0.141 AC: 7505 AN: 53288

Middle Eastern (MID) AF: 0.153 AC: 876 AN: 5740

European-Non Finnish (NFE) AF: 0.133 AC: 147128 AN: 1109666

Other (OTH) AF: 0.142 AC: 8562 AN: 60190

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

African (AFR) AF: 0.0721 AC: 2993 AN: 41534

American (AMR) AF: 0.0948 AC: 1449 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3470

East Asian (EAS) AF: 0.122 AC: 633 AN: 5174

South Asian (SAS) AF: 0.195 AC: 939 AN: 4826

European-Finnish (FIN) AF: 0.133 AC: 1410 AN: 10594

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9103 AN: 67996

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.131 Hom.: 2395

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
PhyloP100		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292307; hg19: chr10-75549916; COSMIC: COSV67131693; COSMIC: COSV67131693;