10-79201626-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_020338.4(ZMIZ1):c.-7G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00299 in 1,613,434 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (10 hom.)
• Consequence: ZMIZ1 NM_020338.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.87

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=-0.21).
• BP6: Variant 10-79201626-G-A is Benign according to our data. Variant chr10-79201626-G-A is described in ClinVar as [Benign]. Clinvar id is 2640629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00269 (409/152258) while in subpopulation NFE AF= 0.00387 (263/68016). AF 95% confidence interval is 0.00348. There are 1 homozygotes in gnomad4. There are 203 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 409 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMIZ1	NM_020338.4	c.-7G>A		5_prime_UTR_variant	5/25	ENST00000334512.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.-7G>A		5_prime_UTR_variant	5/25	5	NM_020338.4	P1

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 409 AN: 152140 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00830

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00387

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00322 AC: 807 AN: 250654 Hom.: 2 AF XY: 0.00309 AC XY: 419 AN XY: 135542

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0000983

Gnomad FIN exome AF: 0.00931

Gnomad NFE exome AF: 0.00474

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.00302 AC: 4420 AN: 1461176 Hom.: 10 Cov.: 31 AF XY: 0.00296 AC XY: 2154 AN XY: 726918

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000739

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00987

Gnomad4 NFE exome AF: 0.00322

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.00269 AC: 409 AN: 152258 Hom.: 1 Cov.: 33 AF XY: 0.00273 AC XY: 203 AN XY: 74434

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00830

Gnomad4 NFE AF: 0.00387

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00290 Hom.: 0

Bravo AF: 0.00224

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00218

EpiControl AF: 0.00326

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ZMIZ1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
Cadd	Benign	21
Dann	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs190817159; hg19: chr10-80961383;