10-79257338-G-C

Variant names:

• chr10-79257338-G-C
• rs1250533
• NM_020338.4:c.281-19843G>C

Variant summary

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

The NM_020338.4(ZMIZ1):​c.281-19843G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,186 control chromosomes in the GnomAD database, including 40,403 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 0.73 (40403 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 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.281-19843G>C		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.281-19843G>C		intron	N/A	ENSP00000334474.5
	ZMIZ1	ENST00000472035.5	TSL:2	n.70+13600G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110361 AN: 152068 Hom.: 40358 Cov.: 33

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.726 AC: 110461 AN: 152186 Hom.: 40403 Cov.: 33 AF XY: 0.730 AC XY: 54287 AN XY: 74404

African (AFR) AF: 0.777 AC: 32237 AN: 41510

American (AMR) AF: 0.683 AC: 10453 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2283 AN: 3470

East Asian (EAS) AF: 0.918 AC: 4757 AN: 5182

South Asian (SAS) AF: 0.718 AC: 3462 AN: 4820

European-Finnish (FIN) AF: 0.779 AC: 8264 AN: 10602

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46696 AN: 67984

Other (OTH) AF: 0.716 AC: 1514 AN: 2116

Alfa AF: 0.697 Hom.: 4605

Bravo AF: 0.721

Asia WGS AF: 0.807 AC: 2808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.81
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs1250533; hg19: chr10-81017095;