NM_020338.4:c.-50+3687G>C

Variant names:

• chr10-79165820-G-C
• rs7916441
• NM_020338.4:c.-50+3687G>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.-50+3687G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,794 control chromosomes in the GnomAD database, including 11,862 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 (11862 hom., cov: 34)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• Publications: 17 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

ENSG00000294199 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 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.-50+3687G>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.-50+3687G>C		intron	N/A	ENSP00000334474.5
	ENSG00000294199	ENST00000721844.1		n.152+1003C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59239 AN: 151676 Hom.: 11857 Cov.: 34

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.416

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.390 AC: 59268 AN: 151794 Hom.: 11862 Cov.: 34 AF XY: 0.389 AC XY: 28851 AN XY: 74172

African (AFR) AF: 0.359 AC: 14847 AN: 41386

American (AMR) AF: 0.357 AC: 5452 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1275 AN: 3466

East Asian (EAS) AF: 0.275 AC: 1405 AN: 5116

South Asian (SAS) AF: 0.310 AC: 1486 AN: 4798

European-Finnish (FIN) AF: 0.440 AC: 4652 AN: 10572

Middle Eastern (MID) AF: 0.420 AC: 121 AN: 288

European-Non Finnish (NFE) AF: 0.427 AC: 28961 AN: 67882

Other (OTH) AF: 0.379 AC: 797 AN: 2104

Alfa AF: 0.401 Hom.: 1521

Bravo AF: 0.382

Asia WGS AF: 0.283 AC: 981 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.85
PhyloP100		0.57
Mutation Taster		=99/1	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: rs7916441; hg19: chr10-80925577;