NM_020338.4:c.2836-1268A>G

Variant names:

• chr10-79309656-A-G
• rs942789
• NM_020338.4:c.2836-1268A>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.2836-1268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,220 control chromosomes in the GnomAD database, including 47,363 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 0.78 (47363 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.2836-1268A>G		intron_variant	Intron 23 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.2836-1268A>G		intron_variant	Intron 23 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119203 AN: 152102 Hom.: 47313 Cov.: 33

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.784 AC: 119308 AN: 152220 Hom.: 47363 Cov.: 33 AF XY: 0.779 AC XY: 57940 AN XY: 74412

African (AFR) AF: 0.900 AC: 37417 AN: 41554

American (AMR) AF: 0.826 AC: 12641 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2883 AN: 3468

East Asian (EAS) AF: 0.600 AC: 3097 AN: 5162

South Asian (SAS) AF: 0.696 AC: 3359 AN: 4824

European-Finnish (FIN) AF: 0.688 AC: 7295 AN: 10596

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50038 AN: 68000

Other (OTH) AF: 0.808 AC: 1708 AN: 2114

Alfa AF: 0.740 Hom.: 33584

Bravo AF: 0.801

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.78
PhyloP100		-1.3
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: rs942789; hg19: chr10-81069413;