Genetic Variant ZMIZ1:c.2835+152C>G (chr10-79307723-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020338.4(ZMIZ1):c.2835+152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 850,954 control chromosomes in the GnomAD database, including 62,893 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.

Frequency

Genomes: 𝑓 0.30 ( 8496 hom., cov: 31)

Exomes 𝑓: 0.38 ( 54397 hom. )

Consequence

ZMIZ1
NM_020338.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.615

Publications

13 publications found

Variant links:

Genes affected

ZMIZ1 (HGNC:16493): (zinc finger MIZ-type containing 1) This gene encodes a member of the PIAS (protein inhibitor of activated STAT) family of proteins. The encoded protein regulates the activity of various transcription factors, including the androgen receptor, Smad3/4, and p53. The encoded protein may also play a role in sumoylation. A translocation between this locus on chromosome 10 and the protein tyrosine kinase ABL1 locus on chromosome 9 has been associated with acute lymphoblastic leukemia. [provided by RefSeq, Mar 2010]

ZMIZ1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ZMIZ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4 link	c.2835+152C>G		intron_variant	Intron 23 of 24	ENST00000334512.10	NP_065071.1	Q9ULJ6-1A0JLS3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10 link	c.2835+152C>G		intron_variant	Intron 23 of 24	5	NM_020338.4	ENSP00000334474.5		Q9ULJ6-1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45243

AN:

151856

Hom.:

8491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0731

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.381

AC:

266127

AN:

698980

Hom.:

54397

AF XY:

0.381

AC XY:

135075

AN XY:

354624

show subpopulations

African (AFR)

AF:

0.0659

AC:

1103

AN:

16736

American (AMR)

AF:

0.259

AC:

4254

AN:

16420

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

3643

AN:

15186

East Asian (EAS)

AF:

0.451

AC:

13455

AN:

29840

South Asian (SAS)

AF:

0.381

AC:

18970

AN:

49732

European-Finnish (FIN)

AF:

0.468

AC:

14731

AN:

31452

Middle Eastern (MID)

AF:

0.207

AC:

694

AN:

3358

European-Non Finnish (NFE)

AF:

0.393

AC:

197445

AN:

502046

Other (OTH)

AF:

0.346

AC:

11832

AN:

34210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

8049

16098

24146

32195

40244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4332

8664

12996

17328

21660

<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:

0.298

AC:

45247

AN:

151974

Hom.:

8496

Cov.:

AF XY:

0.304

AC XY:

22577

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0729

AC:

3023

AN:

41476

American (AMR)

AF:

0.277

AC:

4235

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

766

AN:

3468

East Asian (EAS)

AF:

0.414

AC:

2130

AN:

5140

South Asian (SAS)

AF:

0.386

AC:

1859

AN:

4810

European-Finnish (FIN)

AF:

0.482

AC:

5091

AN:

10554

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27165

AN:

67928

Other (OTH)

AF:

0.271

AC:

572

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1462

2924

4387

5849

7311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.240

Hom.:

678

Bravo

AF:

0.270

Asia WGS

AF:

0.337

AC:

1171

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.65

(source)

DANN

Benign

0.40

PhyloP100

-0.61

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over