NM_020338.4:c.281-4406A>G

Variant names:

• chr10-79272775-A-G
• rs1250546
• NM_020338.4:c.281-4406A>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.281-4406A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,064 control chromosomes in the GnomAD database, including 10,619 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 0.36 (10619 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 56 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.281-4406A>G		intron_variant	Intron 7 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.281-4406A>G		intron_variant	Intron 7 of 24	5	NM_020338.4	ENSP00000334474.5
ZMIZ1	ENST00000472035.5	n.71-4406A>G		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55396 AN: 151946 Hom.: 10612 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.364 AC: 55416 AN: 152064 Hom.: 10619 Cov.: 33 AF XY: 0.368 AC XY: 27356 AN XY: 74350

African (AFR) AF: 0.245 AC: 10158 AN: 41470

American (AMR) AF: 0.335 AC: 5121 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1074 AN: 3472

East Asian (EAS) AF: 0.462 AC: 2388 AN: 5174

South Asian (SAS) AF: 0.429 AC: 2069 AN: 4822

European-Finnish (FIN) AF: 0.467 AC: 4936 AN: 10572

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28511 AN: 67958

Other (OTH) AF: 0.342 AC: 721 AN: 2108

Alfa AF: 0.391 Hom.: 19838

Bravo AF: 0.350

Asia WGS AF: 0.387 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.33
PhyloP100		-0.23
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: rs1250546; hg19: chr10-81032532;