rs781655188

Variant names:

• chr19-13799738-C-T
• rs781655188
• NM_001367834.3:c.172C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-13799738-C-T
• chr19-13799738-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001367834.3(ZSWIM4):​c.172C>T​(p.Arg58Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ZSWIM4 NM_001367834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.251
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367834.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM4	NM_001367834.3	MANE Select	c.172C>T	p.Arg58Trp	missense	Exon 2 of 14	NP_001354763.1	K7ERJ6
	ZSWIM4	NM_023072.3		c.172C>T	p.Arg58Trp	missense	Exon 2 of 13	NP_075560.2	Q9H7M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM4	ENST00000590508.6	TSL:2 MANE Select	c.172C>T	p.Arg58Trp	missense	Exon 2 of 14	ENSP00000468285.2	K7ERJ6
	ZSWIM4	ENST00000938264.1		c.220C>T	p.Arg74Trp	missense	Exon 3 of 15	ENSP00000608323.1
	ZSWIM4	ENST00000938266.1		c.172C>T	p.Arg58Trp	missense	Exon 2 of 14	ENSP00000608325.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152190 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000518 AC: 13 AN: 251118 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461698 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727132

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152190 Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74360

African (AFR) AF: 0.0000724 AC: 3 AN: 41446

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.25
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.19
Sift	Uncertain	0.026	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.74
MVP		0.48
MPC		1.4
ClinPred		0.79	D
GERP RS		4.4
Varity_R		0.21
gMVP		0.66
Mutation Taster		=84/16	polymorphism

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: rs781655188; hg19: chr19-13910552; COSMIC: COSV54326741; COSMIC: COSV54326741;