NM_020338.4:c.-131+5167A>C

Variant names:

• chr10-79144944-A-C
• rs780157
• NM_020338.4:c.-131+5167A>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.-131+5167A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 148,530 control chromosomes in the GnomAD database, including 25,847 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 0.59 (25847 hom., cov: 28)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.13
• Publications: 3 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 = 0.696 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	NM_020338.4	MANE Select	c.-131+5167A>C		intron	N/A	NP_065071.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ1	ENST00000334512.10	TSL:5 MANE Select	c.-131+5167A>C		intron	N/A	ENSP00000334474.5
	ZMIZ1	ENST00000928256.1		c.-50+5167A>C		intron	N/A	ENSP00000598315.1
	ZMIZ1	ENST00000880201.1		c.-128+5167A>C		intron	N/A	ENSP00000550260.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 87291 AN: 148410 Hom.: 25812 Cov.: 28

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.588 AC: 87382 AN: 148530 Hom.: 25847 Cov.: 28 AF XY: 0.584 AC XY: 42351 AN XY: 72524

African (AFR) AF: 0.703 AC: 28614 AN: 40706

American (AMR) AF: 0.613 AC: 9225 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1856 AN: 3378

East Asian (EAS) AF: 0.327 AC: 1602 AN: 4896

South Asian (SAS) AF: 0.571 AC: 2632 AN: 4606

European-Finnish (FIN) AF: 0.515 AC: 5296 AN: 10282

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 36196 AN: 66354

Other (OTH) AF: 0.597 AC: 1234 AN: 2066

Alfa AF: 0.544 Hom.: 44994

Bravo AF: 0.588

Asia WGS AF: 0.493 AC: 1716 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	0.038
DANN	Benign	0.47
PhyloP100		-4.1
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: rs780157; hg19: chr10-80904701;