10-79213363-C-T

Variant names:

• chr10-79213363-C-T
• rs1250580
• NM_020338.4:c.175-2806C>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.175-2806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,998 control chromosomes in the GnomAD database, including 28,725 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 0.61 (28725 hom., cov: 32)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.175-2806C>T		intron_variant	Intron 6 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.175-2806C>T		intron_variant	Intron 6 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92945 AN: 151880 Hom.: 28707 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.612 AC: 93016 AN: 151998 Hom.: 28725 Cov.: 32 AF XY: 0.605 AC XY: 44952 AN XY: 74258

African (AFR) AF: 0.611 AC: 25355 AN: 41478

American (AMR) AF: 0.589 AC: 9010 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2448 AN: 5154

South Asian (SAS) AF: 0.555 AC: 2672 AN: 4818

European-Finnish (FIN) AF: 0.559 AC: 5899 AN: 10554

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43828 AN: 67920

Other (OTH) AF: 0.595 AC: 1260 AN: 2116

Alfa AF: 0.630 Hom.: 20238

Bravo AF: 0.614

Asia WGS AF: 0.563 AC: 1962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.53
PhyloP100		-0.94
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: rs1250580; hg19: chr10-80973120;