Genetic Variant NM_001367799.1:c.3371G>A (chr10-73797209-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001367799.1(ZSWIM8):c.3371G>A(p.Ser1124Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

ZSWIM8
NM_001367799.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

Publications

1 publications found

Variant links:

Genes affected

ZSWIM8 (HGNC:23528): (zinc finger SWIM-type containing 8) Enables ubiquitin ligase-substrate adaptor activity. Involved in positive regulation of miRNA catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZSWIM8 links:

ZSWIM8-AS1 (HGNC:45103): (ZSWIM8 antisense RNA 1)

ZSWIM8-AS1 links:

ENSG00000272916 (HGNC:):

ENSG00000272916 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1173403).

BS2

High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367799.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSWIM8	NM_001367799.1	MANE Select	c.3371G>A	p.Ser1124Asn	missense	Exon 17 of 26	NP_001354728.1	S4R410
ZSWIM8	NM_001242488.2		c.3356G>A	p.Ser1119Asn	missense	Exon 17 of 26	NP_001229417.1	A7E2V4-2
ZSWIM8	NM_015037.4		c.3371G>A	p.Ser1124Asn	missense	Exon 17 of 26	NP_055852.2	A7E2V4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSWIM8	ENST00000604729.6	TSL:5 MANE Select	c.3371G>A	p.Ser1124Asn	missense	Exon 17 of 26	ENSP00000474944.1	S4R410
ZSWIM8	ENST00000605216.5	TSL:1	c.3356G>A	p.Ser1119Asn	missense	Exon 17 of 26	ENSP00000474748.1	A7E2V4-1
ZSWIM8	ENST00000603187.5	TSL:1	c.1373G>A	p.Ser458Asn	missense	Exon 8 of 17	ENSP00000474766.1	S4R3U7

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000882

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000402

AC:

AN:

249052

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000753

AC:

110

AN:

1461688

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000179

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000872

AC:

AN:

1111866

Other (OTH)

AF:

0.0000663

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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:

0.0000657

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41452

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68024

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.0000965

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Benign

0.093

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.017

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0038

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.1

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.52

REVEL

Benign

0.12

Sift

Benign

0.47

Sift4G

Benign

0.53

Polyphen

0.0010

Vest4

0.17

MVP

0.043

MPC

0.71

ClinPred

0.039

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.28

Mutation Taster

=93/7

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