10-79232624-C-T

Variant names:

• chr10-79232624-C-T
• rs1574190
• NM_020338.4:c.280+16350C>T

Variant summary

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

The NM_020338.4(ZMIZ1):​c.280+16350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,964 control chromosomes in the GnomAD database, including 7,687 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 0.31 (7687 hom., cov: 31)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.280+16350C>T		intron_variant	Intron 7 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.280+16350C>T		intron_variant	Intron 7 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46397 AN: 151846 Hom.: 7684 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.305 AC: 46420 AN: 151964 Hom.: 7687 Cov.: 31 AF XY: 0.300 AC XY: 22315 AN XY: 74298

African (AFR) AF: 0.194 AC: 8024 AN: 41444

American (AMR) AF: 0.294 AC: 4498 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1135 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1051 AN: 5152

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4820

European-Finnish (FIN) AF: 0.288 AC: 3047 AN: 10566

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.389 AC: 26442 AN: 67926

Other (OTH) AF: 0.300 AC: 633 AN: 2112

Alfa AF: 0.348 Hom.: 7295

Bravo AF: 0.301

Asia WGS AF: 0.230 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.82
PhyloP100		-1.8
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: rs1574190; hg19: chr10-80992381;