rs881406

Variant names:

• chr10-79103198-G-A
• rs881406
• NM_020338.4:c.-336-15717G>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.-336-15717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,096 control chromosomes in the GnomAD database, including 1,832 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 0.14 (1832 hom., cov: 32)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38
• Publications: 2 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=-0.51).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.-336-15717G>A		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.-336-15717G>A		intron_variant	Intron 1 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21277 AN: 151978 Hom.: 1826 Cov.: 32

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.140 AC: 21286 AN: 152096 Hom.: 1832 Cov.: 32 AF XY: 0.140 AC XY: 10411 AN XY: 74348

African (AFR) AF: 0.0607 AC: 2518 AN: 41496

American (AMR) AF: 0.237 AC: 3617 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.111 AC: 572 AN: 5158

South Asian (SAS) AF: 0.0619 AC: 298 AN: 4816

European-Finnish (FIN) AF: 0.152 AC: 1615 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11644 AN: 67964

Other (OTH) AF: 0.159 AC: 336 AN: 2110

Alfa AF: 0.150 Hom.: 757

Bravo AF: 0.149

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs881406; hg19: chr10-80862955;