Genetic Variant ZMIZ1:c.-50+1972C>A (chr10-79164105-C-A) – 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.-50+1972C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,006 control chromosomes in the GnomAD database, including 11,802 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 0.39 ( 11802 hom., cov: 32)

Consequence

ZMIZ1
NM_020338.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

15 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:

ENSG00000294199 (HGNC:):

ENSG00000294199 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=-0.47).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4 link	c.-50+1972C>A		intron_variant	Intron 4 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.-50+1972C>A		intron_variant	Intron 4 of 24	5	NM_020338.4	ENSP00000334474.5		Q9ULJ6-1
ENSG00000294199	ENST00000721844.1 link	n.330+6G>T		splice_region_variant, intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.389

AC:

59099

AN:

151890

Hom.:

11798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.389

AC:

59126

AN:

152006

Hom.:

11802

Cov.:

AF XY:

0.387

AC XY:

28781

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.356

AC:

14777

AN:

41456

American (AMR)

AF:

0.356

AC:

5432

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1268

AN:

3470

East Asian (EAS)

AF:

0.276

AC:

1422

AN:

5156

South Asian (SAS)

AF:

0.308

AC:

1481

AN:

4816

European-Finnish (FIN)

AF:

0.438

AC:

4623

AN:

10564

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.426

AC:

28935

AN:

67952

Other (OTH)

AF:

0.376

AC:

793

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1851

3702

5554

7405

9256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.405

Hom.:

5311

Bravo

AF:

0.381

Asia WGS

AF:

0.283

AC:

986

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over