NM_020338.4:c.280+23838T>C

Variant names:

• chr10-79240112-T-C
• rs1749849
• NM_020338.4:c.280+23838T>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.280+23838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,078 control chromosomes in the GnomAD database, including 17,465 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 0.46 (17465 hom., cov: 32)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 12 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=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.280+23838T>C		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+23838T>C		intron_variant	Intron 7 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70330 AN: 151962 Hom.: 17453 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.463 AC: 70390 AN: 152078 Hom.: 17465 Cov.: 32 AF XY: 0.464 AC XY: 34465 AN XY: 74332

African (AFR) AF: 0.288 AC: 11928 AN: 41476

American (AMR) AF: 0.446 AC: 6822 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1360 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2300 AN: 5168

South Asian (SAS) AF: 0.587 AC: 2831 AN: 4824

European-Finnish (FIN) AF: 0.546 AC: 5775 AN: 10574

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37937 AN: 67952

Other (OTH) AF: 0.447 AC: 945 AN: 2114

Alfa AF: 0.523 Hom.: 69583

Bravo AF: 0.441

Asia WGS AF: 0.527 AC: 1835 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.9
DANN	Benign	0.65
PhyloP100		0.21
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: rs1749849; hg19: chr10-80999869;