Genetic Variant ZSWIM4:p.Arg102Cys (chr19-13799870-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001367834.3(ZSWIM4):c.304C>T(p.Arg102Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000707 in 1,613,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

ZSWIM4
NM_001367834.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Publications

1 publications found

Variant links:

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]

ZSWIM4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.824

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.304C>T	p.Arg102Cys	missense	Exon 2 of 14	NP_001354763.1	K7ERJ6
	ZSWIM4	NM_023072.3		c.304C>T	p.Arg102Cys	missense	Exon 2 of 13	NP_075560.2	Q9H7M6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSWIM4	ENST00000590508.6	TSL:2 MANE Select	c.304C>T	p.Arg102Cys	missense	Exon 2 of 14	ENSP00000468285.2	K7ERJ6
ZSWIM4	ENST00000938264.1		c.352C>T	p.Arg118Cys	missense	Exon 3 of 15	ENSP00000608323.1
ZSWIM4	ENST00000938266.1		c.304C>T	p.Arg102Cys	missense	Exon 2 of 14	ENSP00000608325.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

249806

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000732

AC:

107

AN:

1461116

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

726880

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52724

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000926

AC:

103

AN:

1111962

Other (OTH)

AF:

0.0000166

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000388

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.2

PhyloP100

3.1

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.41

Sift

Uncertain

0.020

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.92

MVP

0.65

MPC

1.7

ClinPred

0.80

GERP RS

4.3

Varity_R

0.15

gMVP

0.90

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over