rs12610873

Positions:

• chr19-13831773-G-A
• chr19-13831773-G-C

Variant summary

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

The NM_001367834.3(ZSWIM4):​c.*723G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,106 control chromosomes in the GnomAD database, including 8,556 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 0.33 (8534 hom., cov: 29)
  • Exomes 𝑓: 0.40 (22 hom.)
• Consequence: ZSWIM4 NM_001367834.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

Genes affected

ZSWIM4 (HGNC:25704): (zinc finger SWIM-type containing 4) Predicted to enable zinc ion binding activity. Predicted to be part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR23AHG (HGNC:27620): (miR-23a/27a/24-2 cluster host gene)

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 (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSWIM4	NM_001367834.3	c.*723G>A		3_prime_UTR_variant	14/14	ENST00000590508.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSWIM4	ENST00000590508.6	c.*723G>A		3_prime_UTR_variant	14/14	2	NM_001367834.3	P1
MIR23AHG	ENST00000587762.2	n.11156C>T		non_coding_transcript_exon_variant	1/1
ZSWIM4	ENST00000254323.6	c.*723G>A		3_prime_UTR_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50567 AN: 151646 Hom.: 8532 Cov.: 29

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.398 AC: 137 AN: 344 Hom.: 22 Cov.: 0 AF XY: 0.399 AC XY: 87 AN XY: 218

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.333 AC: 50586 AN: 151762 Hom.: 8534 Cov.: 29 AF XY: 0.332 AC XY: 24625 AN XY: 74114

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.274

Alfa AF: 0.311 Hom.: 11171

Bravo AF: 0.325

Asia WGS AF: 0.305 AC: 1059 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	0.63
DANN	Benign	0.83

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: rs12610873; hg19: chr19-13942587; COSMIC: COSV54323712; COSMIC: COSV54323712;