10-79283615-G-C

Variant names:

• chr10-79283615-G-C
• rs1108616
• NM_020338.4:c.426-6160G>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.426-6160G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,986 control chromosomes in the GnomAD database, including 19,138 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 0.50 (19138 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 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.426-6160G>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.426-6160G>C		intron	N/A	ENSP00000334474.5
	ZMIZ1	ENST00000472035.5	TSL:2	n.216-6160G>C		intron	N/A
	ZMIZ1	ENST00000478357.1	TSL:2	n.148-6160G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75902 AN: 151868 Hom.: 19118 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.500 AC: 75954 AN: 151986 Hom.: 19138 Cov.: 33 AF XY: 0.503 AC XY: 37365 AN XY: 74314

African (AFR) AF: 0.543 AC: 22488 AN: 41430

American (AMR) AF: 0.477 AC: 7281 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1282 AN: 3468

East Asian (EAS) AF: 0.660 AC: 3417 AN: 5180

South Asian (SAS) AF: 0.526 AC: 2536 AN: 4818

European-Finnish (FIN) AF: 0.532 AC: 5613 AN: 10550

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31898 AN: 67950

Other (OTH) AF: 0.459 AC: 968 AN: 2110

Alfa AF: 0.328 Hom.: 773

Bravo AF: 0.498

Asia WGS AF: 0.530 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.70
DANN	Benign	0.52
PhyloP100		-1.6
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: rs1108616; hg19: chr10-81043372;