rs4980022

Variant names:

• chr10-79074928-C-T
• rs4980022
• NM_020338.4:c.-337+5658C>T

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+5658C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,200 control chromosomes in the GnomAD database, including 13,451 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 (13451 hom., cov: 35)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 3 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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.-337+5658C>T		intron_variant	Intron 1 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.-337+5658C>T		intron_variant	Intron 1 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60720 AN: 152082 Hom.: 13446 Cov.: 35

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.399 AC: 60733 AN: 152200 Hom.: 13451 Cov.: 35 AF XY: 0.397 AC XY: 29550 AN XY: 74408

African (AFR) AF: 0.234 AC: 9727 AN: 41530

American (AMR) AF: 0.325 AC: 4977 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1647 AN: 3468

East Asian (EAS) AF: 0.164 AC: 849 AN: 5174

South Asian (SAS) AF: 0.358 AC: 1727 AN: 4826

European-Finnish (FIN) AF: 0.534 AC: 5658 AN: 10592

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34739 AN: 67992

Other (OTH) AF: 0.392 AC: 828 AN: 2114

Alfa AF: 0.471 Hom.: 10877

Bravo AF: 0.374

Asia WGS AF: 0.218 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-2.6
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: rs4980022; hg19: chr10-80834685;