chr10-79175326-G-C

Variant names:

• chr10-79175326-G-C
• rs780148
• NM_020338.4:c.-50+13193G>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+13193G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,168 control chromosomes in the GnomAD database, including 35,763 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 0.67 (35763 hom., cov: 34)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 9 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	NM_020338.4	MANE Select	c.-50+13193G>C		intron	N/A	NP_065071.1	Q9ULJ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	ENST00000334512.10	TSL:5 MANE Select	c.-50+13193G>C		intron	N/A	ENSP00000334474.5	Q9ULJ6-1
	ZMIZ1	ENST00000928256.1		c.-49-26258G>C		intron	N/A	ENSP00000598315.1
	ZMIZ1	ENST00000880201.1		c.-50+13193G>C		intron	N/A	ENSP00000550260.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101831 AN: 152050 Hom.: 35696 Cov.: 34

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.670 AC: 101959 AN: 152168 Hom.: 35763 Cov.: 34 AF XY: 0.678 AC XY: 50396 AN XY: 74368

African (AFR) AF: 0.864 AC: 35905 AN: 41572

American (AMR) AF: 0.698 AC: 10673 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3468

East Asian (EAS) AF: 0.900 AC: 4640 AN: 5156

South Asian (SAS) AF: 0.640 AC: 3079 AN: 4810

European-Finnish (FIN) AF: 0.654 AC: 6921 AN: 10586

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36630 AN: 67966

Other (OTH) AF: 0.650 AC: 1376 AN: 2116

Alfa AF: 0.331 Hom.: 403

Bravo AF: 0.681

Asia WGS AF: 0.779 AC: 2707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.36
PhyloP100		-2.3
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: rs780148; hg19: chr10-80935083;