rs1250544

Variant names:

• chr10-79273128-G-A
• rs1250544
• NM_020338.4:c.281-4053G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-79273128-G-A
• chr10-79273128-G-C
• chr10-79273128-G-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.281-4053G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,008 control chromosomes in the GnomAD database, including 8,184 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 0.32 (8184 hom., cov: 32)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 31 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 (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.281-4053G>A		intron_variant	Intron 7 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.281-4053G>A		intron_variant	Intron 7 of 24	5	NM_020338.4	ENSP00000334474.5
ZMIZ1	ENST00000472035.5	n.71-4053G>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48372 AN: 151890 Hom.: 8181 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.318 AC: 48387 AN: 152008 Hom.: 8184 Cov.: 32 AF XY: 0.323 AC XY: 24005 AN XY: 74284

African (AFR) AF: 0.207 AC: 8575 AN: 41488

American (AMR) AF: 0.284 AC: 4344 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2324 AN: 5164

South Asian (SAS) AF: 0.391 AC: 1881 AN: 4816

European-Finnish (FIN) AF: 0.435 AC: 4590 AN: 10548

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24879 AN: 67914

Other (OTH) AF: 0.283 AC: 599 AN: 2114

Alfa AF: 0.334 Hom.: 2819

Bravo AF: 0.304

Asia WGS AF: 0.368 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.55
PhyloP100		-0.51
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: rs1250544; hg19: chr10-81032885;