rs12355688

Variant names:

• chr10-79295869-C-T
• rs12355688
• NM_020338.4:c.1231-602C>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.1231-602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,320 control chromosomes in the GnomAD database, including 1,474 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 0.12 (1474 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 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.1231-602C>T		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.1231-602C>T		intron	N/A	ENSP00000334474.5
	ZMIZ1	ENST00000478357.1	TSL:2	n.3186C>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17473 AN: 151978 Hom.: 1468 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0999

GnomAD4 exome AF: 0.0495 AC: 11 AN: 222 Hom.: 0 Cov.: 0 AF XY: 0.0597 AC XY: 8 AN XY: 134

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.0758 AC: 5 AN: 66

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0439 AC: 5 AN: 114

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.115 AC: 17503 AN: 152098 Hom.: 1474 Cov.: 32 AF XY: 0.118 AC XY: 8740 AN XY: 74346

African (AFR) AF: 0.227 AC: 9404 AN: 41452

American (AMR) AF: 0.0839 AC: 1284 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1238 AN: 5154

South Asian (SAS) AF: 0.142 AC: 683 AN: 4810

European-Finnish (FIN) AF: 0.0736 AC: 779 AN: 10588

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0511 AC: 3475 AN: 68000

Other (OTH) AF: 0.101 AC: 214 AN: 2114

Alfa AF: 0.0772 Hom.: 1627

Bravo AF: 0.122

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12355688; hg19: chr10-81055626;