NM_020338.4:c.-49-18620A>G

Variant names:

• chr10-79182964-A-G
• rs703982
• NM_020338.4:c.-49-18620A>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.-49-18620A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,114 control chromosomes in the GnomAD database, including 8,935 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 0.32 (8935 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807
• Publications: 16 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 = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.-49-18620A>G		intron_variant	Intron 4 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.-49-18620A>G		intron_variant	Intron 4 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49271 AN: 151996 Hom.: 8930 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.324 AC: 49277 AN: 152114 Hom.: 8935 Cov.: 33 AF XY: 0.323 AC XY: 24017 AN XY: 74370

African (AFR) AF: 0.146 AC: 6042 AN: 41504

American (AMR) AF: 0.383 AC: 5855 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1812 AN: 5166

South Asian (SAS) AF: 0.319 AC: 1536 AN: 4810

European-Finnish (FIN) AF: 0.364 AC: 3858 AN: 10590

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27791 AN: 67970

Other (OTH) AF: 0.323 AC: 683 AN: 2114

Alfa AF: 0.372 Hom.: 32039

Bravo AF: 0.319

Asia WGS AF: 0.322 AC: 1122 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	0.30
DANN	Benign	0.56
PhyloP100		-0.81
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: rs703982; hg19: chr10-80942721;