chr10-79298270-A-G

Variant names:

• chr10-79298270-A-G
• rs1250552
• NM_020338.4:c.1492-136A>G

Variant summary

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

The NM_020338.4(ZMIZ1):​c.1492-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 966,952 control chromosomes in the GnomAD database, including 128,478 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 0.55 (24530 hom., cov: 32)
  • Exomes 𝑓: 0.50 (103948 hom.)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 48 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.1492-136A>G		intron_variant	Intron 14 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.1492-136A>G		intron_variant	Intron 14 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84199 AN: 151824 Hom.: 24477 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.498 AC: 405629 AN: 815010 Hom.: 103948 AF XY: 0.497 AC XY: 206666 AN XY: 415848

African (AFR) AF: 0.718 AC: 12232 AN: 17046

American (AMR) AF: 0.470 AC: 10248 AN: 21790

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 5316 AN: 15562

East Asian (EAS) AF: 0.705 AC: 21574 AN: 30610

South Asian (SAS) AF: 0.565 AC: 31291 AN: 55350

European-Finnish (FIN) AF: 0.569 AC: 25523 AN: 44842

Middle Eastern (MID) AF: 0.418 AC: 1777 AN: 4254

European-Non Finnish (NFE) AF: 0.474 AC: 278918 AN: 587968

Other (OTH) AF: 0.499 AC: 18750 AN: 37588

GnomAD4 genome AF: 0.555 AC: 84306 AN: 151942 Hom.: 24530 Cov.: 32 AF XY: 0.561 AC XY: 41621 AN XY: 74244

African (AFR) AF: 0.715 AC: 29615 AN: 41428

American (AMR) AF: 0.489 AC: 7474 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3470

East Asian (EAS) AF: 0.698 AC: 3600 AN: 5154

South Asian (SAS) AF: 0.577 AC: 2783 AN: 4824

European-Finnish (FIN) AF: 0.576 AC: 6101 AN: 10588

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31930 AN: 67870

Other (OTH) AF: 0.506 AC: 1068 AN: 2112

Alfa AF: 0.490 Hom.: 71689

Bravo AF: 0.556

Asia WGS AF: 0.615 AC: 2139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.47
PhyloP100		-0.10
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: rs1250552; hg19: chr10-81058027; COSMIC: COSV57905856; COSMIC: COSV57905856;