rs12571751

Variant names:

• chr10-79182874-A-G
• rs12571751
• NM_020338.4:c.-49-18710A>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.-49-18710A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,090 control chromosomes in the GnomAD database, including 16,535 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 0.46 (16535 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 95 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.-49-18710A>G		intron_variant	Intron 4 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.-49-18710A>G		intron_variant	Intron 4 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70594 AN: 151972 Hom.: 16520 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.464 AC: 70636 AN: 152090 Hom.: 16535 Cov.: 33 AF XY: 0.466 AC XY: 34628 AN XY: 74350

African (AFR) AF: 0.465 AC: 19289 AN: 41480

American (AMR) AF: 0.481 AC: 7355 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2271 AN: 5164

South Asian (SAS) AF: 0.439 AC: 2115 AN: 4822

European-Finnish (FIN) AF: 0.477 AC: 5037 AN: 10564

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31646 AN: 67976

Other (OTH) AF: 0.439 AC: 928 AN: 2116

Alfa AF: 0.462 Hom.: 54485

Bravo AF: 0.462

Asia WGS AF: 0.448 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.17
PhyloP100		-1.4
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: rs12571751; hg19: chr10-80942631;