Variant 19-13830334-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367834.3(ZSWIM4):c.2605T>C(p.Trp869Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZSWIM4
NM_001367834.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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:

MIR23AHG (HGNC:):

MIR23AHG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18829727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSWIM4	NM_001367834.3 linkuse as main transcript	c.2605T>C	p.Trp869Arg	missense_variant	14/14	ENST00000590508.6	NP_001354763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZSWIM4	ENST00000590508.6 linkuse as main transcript	c.2605T>C	p.Trp869Arg	missense_variant	14/14	2	NM_001367834.3	ENSP00000468285.2	K7ERJ6
ZSWIM4	ENST00000254323.6 linkuse as main transcript	c.2254T>C	p.Trp752Arg	missense_variant	13/13	2		ENSP00000254323.2	Q9H7M6
ZSWIM4	ENST00000592227.1 linkuse as main transcript	c.637T>C	p.Trp213Arg	missense_variant	5/5	3		ENSP00000465180.1	K7EJI0
MIR23AHG	ENST00000587762.2 linkuse as main transcript	n.12595A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152246

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461092

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 23, 2023

The c.2254T>C (p.W752R) alteration is located in exon 13 (coding exon 13) of the ZSWIM4 gene. This alteration results from a T to C substitution at nucleotide position 2254, causing the tryptophan (W) at amino acid position 752 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.00028

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

N;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.39

N;.

REVEL

Benign

0.12

Sift

Benign

0.34

T;.

Sift4G

Benign

0.34

T;T

Polyphen

0.026

B;.

Vest4

0.52

MutPred

0.37

Gain of disorder (P = 3e-04);.;

MVP

0.27

MPC

1.0

ClinPred

0.41

GERP RS

4.1

Varity_R

0.18

gMVP

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over