Variant 7-44757148-G-A 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_031449.4(ZMIZ2):c.367G>A(p.Gly123Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 1,595,814 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 1 hom. )

Consequence

ZMIZ2
NM_031449.4 missense, splice_region

Scores

Splicing: ADA: 0.6729

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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:

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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=0.068143725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMIZ2	NM_031449.4 linkuse as main transcript	c.367G>A	p.Gly123Arg	missense_variant, splice_region_variant	4/19	ENST00000309315.9	NP_113637.3	Q8NF64-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMIZ2	ENST00000309315.9 linkuse as main transcript	c.367G>A	p.Gly123Arg	missense_variant, splice_region_variant	4/19	2	NM_031449.4	ENSP00000311778.4		Q8NF64-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000308

AC:

AN:

220810

Hom.:

AF XY:

0.000367

AC XY:

AN XY:

122530

show subpopulations

Gnomad AFR exome

AF:

0.000147

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000648

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.000487

AC:

703

AN:

1443614

Hom.:

Cov.:

AF XY:

0.000491

AC XY:

353

AN XY:

718732

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000210

Gnomad4 NFE exome

AF:

0.000607

Gnomad4 OTH exome

AF:

0.000386

GnomAD4 genome

AF:

0.000164

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000215

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.000315

AC:

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

Feb 13, 2024

The c.367G>A (p.G123R) alteration is located in exon 4 (coding exon 3) of the ZMIZ2 gene. This alteration results from a G to A substitution at nucleotide position 367, causing the glycine (G) at amino acid position 123 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

0.54

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T;T;T;.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.067

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.87

D;.;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.068

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;L;.;L;.

MutationTaster

Benign

0.97

D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

N;D;D;N;D;.

REVEL

Benign

0.080

Sift

Uncertain

0.0030

D;D;D;D;D;.

Sift4G

Uncertain

0.0090

D;D;D;D;D;D

Polyphen

0.010

B;B;B;.;B;.

Vest4

0.41

MutPred

0.32

.;Gain of methylation at G123 (P = 0.0077);Gain of methylation at G123 (P = 0.0077);.;Gain of methylation at G123 (P = 0.0077);Gain of methylation at G123 (P = 0.0077);

MVP

0.068

MPC

0.47

ClinPred

0.087

GERP RS

3.9

Varity_R

0.15

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.67

dbscSNV1_RF

Benign

0.39

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