rs1250565

Variant names:

• chr10-79287258-G-A
• rs1250565
• NM_020338.4:c.426-2517G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020338.4(ZMIZ1):​c.426-2517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,022 control chromosomes in the GnomAD database, including 11,398 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 0.38 (11398 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 10 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 (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.426-2517G>A		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.426-2517G>A		intron_variant	Intron 8 of 24	5	NM_020338.4	ENSP00000334474.5
ZMIZ1	ENST00000472035.5	n.216-2517G>A		intron_variant	Intron 2 of 3	2
ZMIZ1	ENST00000478357.1	n.148-2517G>A		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58115 AN: 151904 Hom.: 11388 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.383 AC: 58165 AN: 152022 Hom.: 11398 Cov.: 33 AF XY: 0.389 AC XY: 28900 AN XY: 74288

African (AFR) AF: 0.426 AC: 17632 AN: 41436

American (AMR) AF: 0.306 AC: 4678 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2258 AN: 5148

South Asian (SAS) AF: 0.444 AC: 2140 AN: 4818

European-Finnish (FIN) AF: 0.484 AC: 5120 AN: 10570

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24467 AN: 67984

Other (OTH) AF: 0.326 AC: 689 AN: 2114

Alfa AF: 0.361 Hom.: 3419

Bravo AF: 0.371

Asia WGS AF: 0.390 AC: 1356 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	6.1
DANN	Benign	0.68
PhyloP100		1.8
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: rs1250565; hg19: chr10-81047015;