10-79176690-T-C

Variant names:

• chr10-79176690-T-C
• rs3862511
• NM_020338.4:c.-50+14557T>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+14557T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 150,310 control chromosomes in the GnomAD database, including 13,196 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 0.35 (13196 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 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+14557T>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+14557T>C		intron	N/A	ENSP00000334474.5	Q9ULJ6-1
	ZMIZ1	ENST00000928256.1		c.-49-24894T>C		intron	N/A	ENSP00000598315.1
	ZMIZ1	ENST00000880201.1		c.-50+14557T>C		intron	N/A	ENSP00000550260.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 52574 AN: 150192 Hom.: 13155 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.350 AC: 52674 AN: 150310 Hom.: 13196 Cov.: 33 AF XY: 0.358 AC XY: 26255 AN XY: 73362

African (AFR) AF: 0.665 AC: 27540 AN: 41396

American (AMR) AF: 0.333 AC: 5058 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3462 AN: 5162

South Asian (SAS) AF: 0.466 AC: 2228 AN: 4784

European-Finnish (FIN) AF: 0.212 AC: 2151 AN: 10134

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10445 AN: 66870

Other (OTH) AF: 0.342 AC: 715 AN: 2090

Alfa AF: 0.202 Hom.: 6455

Bravo AF: 0.370

Asia WGS AF: 0.544 AC: 1885 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.2
DANN	Benign	0.45
PhyloP100		-0.24
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: rs3862511; hg19: chr10-80936447;