dbSNP rs12355688: ZMIZ1:c.1231-602C>T (chr10-79295869-C-T) – 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.1231-602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,320 control chromosomes in the GnomAD database, including 1,474 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 0.12 ( 1474 hom., cov: 32)

Exomes 𝑓: 0.050 ( 0 hom. )

Consequence

ZMIZ1
NM_020338.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.161

Publications

22 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4 link	c.1231-602C>T		intron_variant	Intron 12 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.1231-602C>T		intron_variant	Intron 12 of 24	5	NM_020338.4	ENSP00000334474.5		Q9ULJ6-1
ZMIZ1	ENST00000478357.1 link	n.3186C>T		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17473

AN:

151978

Hom.:

1468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0842

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0736

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0511

Gnomad OTH

AF:

0.0999

GnomAD4 exome

AF:

0.0495

AC:

AN:

222

Hom.:

Cov.:

AF XY:

0.0597

AC XY:

AN XY:

134

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.0758

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0439

AC:

AN:

114

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.115

AC:

17503

AN:

152098

Hom.:

1474

Cov.:

AF XY:

0.118

AC XY:

8740

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.227

AC:

9404

AN:

41452

American (AMR)

AF:

0.0839

AC:

1284

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

356

AN:

3472

East Asian (EAS)

AF:

0.240

AC:

1238

AN:

5154

South Asian (SAS)

AF:

0.142

AC:

683

AN:

4810

European-Finnish (FIN)

AF:

0.0736

AC:

779

AN:

10588

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0511

AC:

3475

AN:

68000

Other (OTH)

AF:

0.101

AC:

214

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

743

1486

2230

2973

3716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.0772

Hom.:

1627

Bravo

AF:

0.122

Asia WGS

AF:

0.189

AC:

657

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.4

(source)

DANN

Benign

0.64

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over