10-79183098-G-C

Variant names:

• chr10-79183098-G-C
• rs703981
• NM_020338.4:c.-49-18486G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020338.4(ZMIZ1):​c.-49-18486G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,050 control chromosomes in the GnomAD database, including 12,196 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 0.39 (12196 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 14 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020338.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	NM_020338.4	MANE Select	c.-49-18486G>C		intron	N/A	NP_065071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	ENST00000334512.10	TSL:5 MANE Select	c.-49-18486G>C		intron	N/A	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58724 AN: 151932 Hom.: 12190 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.386 AC: 58739 AN: 152050 Hom.: 12196 Cov.: 33 AF XY: 0.388 AC XY: 28844 AN XY: 74316

African (AFR) AF: 0.226 AC: 9396 AN: 41506

American (AMR) AF: 0.430 AC: 6577 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1409 AN: 3466

East Asian (EAS) AF: 0.420 AC: 2160 AN: 5146

South Asian (SAS) AF: 0.362 AC: 1743 AN: 4818

European-Finnish (FIN) AF: 0.474 AC: 5010 AN: 10578

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31180 AN: 67932

Other (OTH) AF: 0.375 AC: 791 AN: 2110

Alfa AF: 0.418 Hom.: 1710

Bravo AF: 0.377

Asia WGS AF: 0.376 AC: 1309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		1.2
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: rs703981; hg19: chr10-80942855; COSMIC: COSV57895528;