NM_020338.4:c.281-26088T>G

Variant names:

• chr10-79251093-T-G
• rs1250600
• NM_020338.4:c.281-26088T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020338.4(ZMIZ1):​c.281-26088T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,944 control chromosomes in the GnomAD database, including 32,720 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 0.65 (32720 hom., cov: 31)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 5 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020338.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	NM_020338.4	MANE Select	c.281-26088T>G		intron	N/A	NP_065071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	ENST00000334512.10	TSL:5 MANE Select	c.281-26088T>G		intron	N/A	ENSP00000334474.5
	ZMIZ1	ENST00000472035.5	TSL:2	n.70+7355T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99161 AN: 151826 Hom.: 32677 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.653 AC: 99258 AN: 151944 Hom.: 32720 Cov.: 31 AF XY: 0.657 AC XY: 48766 AN XY: 74244

African (AFR) AF: 0.690 AC: 28580 AN: 41438

American (AMR) AF: 0.597 AC: 9129 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1810 AN: 3464

East Asian (EAS) AF: 0.804 AC: 4128 AN: 5136

South Asian (SAS) AF: 0.681 AC: 3286 AN: 4822

European-Finnish (FIN) AF: 0.704 AC: 7436 AN: 10556

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42845 AN: 67940

Other (OTH) AF: 0.611 AC: 1286 AN: 2104

Alfa AF: 0.635 Hom.: 111055

Bravo AF: 0.647

Asia WGS AF: 0.721 AC: 2507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1250600; hg19: chr10-81010850;