NM_020338.4:c.-50+8549T>C

Variant names:

• chr10-79170682-T-C
• rs703990
• NM_020338.4:c.-50+8549T>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+8549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,158 control chromosomes in the GnomAD database, including 49,973 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 0.81 (49973 hom., cov: 32)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	NM_020338.4	MANE Select	c.-50+8549T>C		intron	N/A	NP_065071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	ENST00000334512.10	TSL:5 MANE Select	c.-50+8549T>C		intron	N/A	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122616 AN: 152040 Hom.: 49932 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.806 AC: 122708 AN: 152158 Hom.: 49973 Cov.: 32 AF XY: 0.799 AC XY: 59396 AN XY: 74376

African (AFR) AF: 0.895 AC: 37174 AN: 41540

American (AMR) AF: 0.728 AC: 11127 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2810 AN: 3472

East Asian (EAS) AF: 0.725 AC: 3755 AN: 5178

South Asian (SAS) AF: 0.580 AC: 2794 AN: 4818

European-Finnish (FIN) AF: 0.777 AC: 8216 AN: 10580

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54265 AN: 67968

Other (OTH) AF: 0.804 AC: 1699 AN: 2112

Alfa AF: 0.798 Hom.: 82534

Bravo AF: 0.809

Asia WGS AF: 0.708 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-1.2
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: rs703990; hg19: chr10-80930439;