rs12355688

Positions:

• chr10-79295869-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.1231-602C>T		intron_variant		ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.1231-602C>T		intron_variant		5	NM_020338.4	ENSP00000334474	P1
ZMIZ1	ENST00000478357.1	n.3186C>T		non_coding_transcript_exon_variant	5/5	2

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

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.0758

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0439

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.0839

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0725 Hom.: 415

Bravo AF: 0.122

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs12355688; hg19: chr10-81055626;