dbSNP rs3735478: ZMIZ2:p.Leu408Phe (chr7-44760577-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031449.4(ZMIZ2):c.1224G>T(p.Leu408Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,632 control chromosomes in the GnomAD database, including 62,384 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4521 hom., cov: 30)

Exomes 𝑓: 0.27 ( 57863 hom. )

Consequence

ZMIZ2
NM_031449.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.748

Variant links:

Genes affected

ZMIZ2 (HGNC:22229): (zinc finger MIZ-type containing 2) ZMIZ2 and ZMIZ1 (MIM 607159) are members of a PIAS (see MIM 603566)-like family of proteins that interact with nuclear hormone receptors. ZMIZ2 interacts with androgen receptor (AR; MIM 313700) and enhances AR-mediated transcription (Huang et al., 2005 [PubMed 16051670]).[supplied by OMIM, May 2010]

ZMIZ2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003502369).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ2	NM_031449.4 link	c.1224G>T	p.Leu408Phe	missense_variant	Exon 9 of 19	ENST00000309315.9	NP_113637.3	Q8NF64-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ2	ENST00000309315.9 link	c.1224G>T	p.Leu408Phe	missense_variant	Exon 9 of 19	2	NM_031449.4	ENSP00000311778.4		Q8NF64-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32590

AN:

151700

Hom.:

4517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0543

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.246

AC:

61348

AN:

249486

Hom.:

8799

AF XY:

0.247

AC XY:

33414

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.0475

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.273

AC:

399113

AN:

1461814

Hom.:

57863

Cov.:

AF XY:

0.271

AC XY:

196727

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0455

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.441

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.215

AC:

32600

AN:

151818

Hom.:

4521

Cov.:

AF XY:

0.220

AC XY:

16286

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.0542

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.173

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.262

Hom.:

11940

Bravo

AF:

0.190

TwinsUK

AF:

0.286

AC:

1060

ALSPAC

AF:

0.295

AC:

1138

ESP6500AA

AF:

0.0550

AC:

232

ESP6500EA

AF:

0.276

AC:

2344

ExAC

AF:

0.241

AC:

29187

Asia WGS

AF:

0.164

AC:

570

AN:

3478

EpiCase

AF:

0.283

EpiControl

AF:

0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;T;T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;.;T;T;T;T

MetaRNN

Benign

0.0035

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;M;M;.;.;.

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.4

N;N;N;N;N;.

REVEL

Benign

0.10

Sift

Uncertain

0.028

D;D;D;D;D;.

Sift4G

Benign

0.25

T;T;T;T;T;T

Polyphen

1.0

D;D;D;.;D;.

Vest4

0.39

MutPred

0.067

.;Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);.;.;Loss of stability (P = 0.0257);

MPC

0.50

ClinPred

0.037

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.071

gMVP

0.24

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over