rs1250569

Variant names:

• chr10-79285450-T-C
• rs1250569
• NM_020338.4:c.426-4325T>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.426-4325T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 455,598 control chromosomes in the GnomAD database, including 52,485 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 0.50 (20311 hom., cov: 33)
  • Exomes 𝑓: 0.45 (32174 hom.)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 23 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.426-4325T>C		intron_variant	Intron 8 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.426-4325T>C		intron_variant	Intron 8 of 24	5	NM_020338.4	ENSP00000334474.5
ZMIZ1	ENST00000472035.5	n.216-4325T>C		intron_variant	Intron 2 of 3	2
ZMIZ1	ENST00000478357.1	n.148-4325T>C		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76429 AN: 151994 Hom.: 20266 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.450

GnomAD2 exomes AF: 0.445 AC: 56914 AN: 127950 AF XY: 0.452

Gnomad AFR exome AF: 0.674

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.494

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.409

GnomAD4 exome AF: 0.452 AC: 137163 AN: 303486 Hom.: 32174 Cov.: 0 AF XY: 0.459 AC XY: 79285 AN XY: 172844

African (AFR) AF: 0.672 AC: 5789 AN: 8616

American (AMR) AF: 0.356 AC: 9692 AN: 27262

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 3234 AN: 10784

East Asian (EAS) AF: 0.488 AC: 4487 AN: 9202

South Asian (SAS) AF: 0.538 AC: 32142 AN: 59716

European-Finnish (FIN) AF: 0.528 AC: 6523 AN: 12364

Middle Eastern (MID) AF: 0.377 AC: 1026 AN: 2720

European-Non Finnish (NFE) AF: 0.429 AC: 68045 AN: 158626

Other (OTH) AF: 0.439 AC: 6225 AN: 14196

GnomAD4 genome AF: 0.503 AC: 76529 AN: 152112 Hom.: 20311 Cov.: 33 AF XY: 0.508 AC XY: 37799 AN XY: 74354

African (AFR) AF: 0.671 AC: 27865 AN: 41504

American (AMR) AF: 0.397 AC: 6071 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1078 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2480 AN: 5170

South Asian (SAS) AF: 0.551 AC: 2652 AN: 4816

European-Finnish (FIN) AF: 0.547 AC: 5780 AN: 10568

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29209 AN: 67982

Other (OTH) AF: 0.454 AC: 956 AN: 2108

Alfa AF: 0.430 Hom.: 8147

Bravo AF: 0.498

Asia WGS AF: 0.495 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.79
PhyloP100		-0.16
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: rs1250569; hg19: chr10-81045207; COSMIC: COSV107400467; COSMIC: COSV107400467;