rs3745453

chr19-13831407-A-G

Variant summary

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

The NM_001367834.3(ZSWIM4):c.*357A>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 0.339 in 201,132 control chromosomes in the GnomAD database, including 12,256 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 0.35 (9901 hom., cov: 31)
  • Exomes 𝑓: 0.29 (2355 hom.)
• Consequence: ZSWIM4 NM_001367834.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612

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 = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSWIM4	NM_001367834.3	c.*357A>G		3_prime_UTR_variant	14/14	ENST00000590508.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSWIM4	ENST00000590508.6	c.*357A>G		3_prime_UTR_variant	14/14	2	NM_001367834.3	P1
MIR23AHG	ENST00000587762.2	n.11522T>C		non_coding_transcript_exon_variant	1/1
ZSWIM4	ENST00000254323.6	c.*357A>G		3_prime_UTR_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53799 AN: 151586 Hom.: 9895 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.291 AC: 14398 AN: 49428 Hom.: 2355 Cov.: 0 AF XY: 0.292 AC XY: 7335 AN XY: 25114

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.355 AC: 53828 AN: 151704 Hom.: 9901 Cov.: 31 AF XY: 0.353 AC XY: 26149 AN XY: 74102

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.297

Alfa AF: 0.318 Hom.: 10018

Bravo AF: 0.350

Asia WGS AF: 0.309 AC: 1074 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	2.5
Dann	Benign	0.55

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: rs3745453; hg19: chr19-13942221; COSMIC: COSV54326338; COSMIC: COSV54326338;