10-79288401-T-G

Variant names:

• chr10-79288401-T-G
• rs942793
• NM_020338.4:c.426-1374T>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.426-1374T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,962 control chromosomes in the GnomAD database, including 12,750 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 0.40 (12750 hom., cov: 32)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	NM_020338.4	MANE Select	c.426-1374T>G		intron	N/A	NP_065071.1	Q9ULJ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	ENST00000334512.10	TSL:5 MANE Select	c.426-1374T>G		intron	N/A	ENSP00000334474.5	Q9ULJ6-1
	ZMIZ1	ENST00000928256.1		c.426-1374T>G		intron	N/A	ENSP00000598315.1
	ZMIZ1	ENST00000880201.1		c.426-1374T>G		intron	N/A	ENSP00000550260.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61121 AN: 151844 Hom.: 12733 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.403 AC: 61174 AN: 151962 Hom.: 12750 Cov.: 32 AF XY: 0.411 AC XY: 30549 AN XY: 74284

African (AFR) AF: 0.441 AC: 18252 AN: 41410

American (AMR) AF: 0.360 AC: 5496 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 890 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3310 AN: 5160

South Asian (SAS) AF: 0.456 AC: 2196 AN: 4816

European-Finnish (FIN) AF: 0.505 AC: 5334 AN: 10562

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24592 AN: 67942

Other (OTH) AF: 0.355 AC: 749 AN: 2112

Alfa AF: 0.373 Hom.: 4621

Bravo AF: 0.396

Asia WGS AF: 0.491 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.86
PhyloP100		-0.014
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: rs942793; hg19: chr10-81048158;