chr10-79288854-C-T

Variant names:

• chr10-79288854-C-T
• rs1782645
• NM_020338.4:c.426-921C>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.426-921C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,046 control chromosomes in the GnomAD database, including 15,832 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 0.45 (15832 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.426-921C>T		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.426-921C>T		intron_variant	Intron 8 of 24	5	NM_020338.4	ENSP00000334474.5
ZMIZ1	ENST00000472035.5	n.216-921C>T		intron_variant	Intron 2 of 3	2
ZMIZ1	ENST00000478357.1	n.148-921C>T		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68455 AN: 151928 Hom.: 15814 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.451 AC: 68503 AN: 152046 Hom.: 15832 Cov.: 33 AF XY: 0.459 AC XY: 34110 AN XY: 74324

African (AFR) AF: 0.490 AC: 20326 AN: 41486

American (AMR) AF: 0.410 AC: 6267 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3295 AN: 5142

South Asian (SAS) AF: 0.497 AC: 2400 AN: 4826

European-Finnish (FIN) AF: 0.547 AC: 5780 AN: 10574

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28121 AN: 67936

Other (OTH) AF: 0.410 AC: 867 AN: 2116

Alfa AF: 0.400 Hom.: 17827

Bravo AF: 0.443

Asia WGS AF: 0.511 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.55
DANN	Benign	0.54
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1782645; hg19: chr10-81048611;