10-79081391-T-C

Variant names:

• chr10-79081391-T-C
• rs704010
• NM_020338.4:c.-337+12121T>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.-337+12121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,120 control chromosomes in the GnomAD database, including 39,367 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 0.71 (39367 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 130 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 (AFR) allele frequency at 95% confidence interval = 0.905 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.-337+12121T>C		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.-337+12121T>C		intron	N/A	ENSP00000334474.5	Q9ULJ6-1
	ZMIZ1	ENST00000928256.1		c.-256+12121T>C		intron	N/A	ENSP00000598315.1
	ZMIZ1	ENST00000880201.1		c.-334+12121T>C		intron	N/A	ENSP00000550260.1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107521 AN: 152000 Hom.: 39308 Cov.: 33

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.708 AC: 107636 AN: 152120 Hom.: 39367 Cov.: 33 AF XY: 0.708 AC XY: 52642 AN XY: 74362

African (AFR) AF: 0.913 AC: 37915 AN: 41544

American (AMR) AF: 0.615 AC: 9397 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2253 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3456 AN: 5158

South Asian (SAS) AF: 0.710 AC: 3423 AN: 4822

European-Finnish (FIN) AF: 0.678 AC: 7179 AN: 10586

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41841 AN: 67954

Other (OTH) AF: 0.668 AC: 1409 AN: 2110

Alfa AF: 0.645 Hom.: 121067

Bravo AF: 0.707

Asia WGS AF: 0.672 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs704010; hg19: chr10-80841148;