chr19-13831407-A-G

Variant names:

• chr19-13831407-A-G
• rs3745453
• NM_001367834.3:c.*357A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZSWIM4	NM_001367834.3	c.*357A>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000590508.6	NP_001354763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM4	ENST00000590508.6	c.*357A>G		3_prime_UTR_variant	Exon 14 of 14	2	NM_001367834.3	ENSP00000468285.2
MIR23AHG	ENST00000587762.2	n.11522T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
ZSWIM4	ENST00000254323.6	c.*357A>G		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000254323.2

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

African (AFR) AF: 0.432 AC: 642 AN: 1486

American (AMR) AF: 0.267 AC: 567 AN: 2120

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 347 AN: 1688

East Asian (EAS) AF: 0.245 AC: 677 AN: 2758

South Asian (SAS) AF: 0.292 AC: 738 AN: 2528

European-Finnish (FIN) AF: 0.327 AC: 956 AN: 2926

Middle Eastern (MID) AF: 0.216 AC: 50 AN: 232

European-Non Finnish (NFE) AF: 0.293 AC: 9531 AN: 32524

Other (OTH) AF: 0.281 AC: 890 AN: 3166

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

African (AFR) AF: 0.465 AC: 19235 AN: 41332

American (AMR) AF: 0.302 AC: 4604 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 906 AN: 3462

East Asian (EAS) AF: 0.236 AC: 1213 AN: 5132

South Asian (SAS) AF: 0.321 AC: 1549 AN: 4820

European-Finnish (FIN) AF: 0.369 AC: 3888 AN: 10526

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21545 AN: 67874

Other (OTH) AF: 0.297 AC: 624 AN: 2100

Alfa AF: 0.320 Hom.: 13233

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
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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