10-79184473-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020338.4(ZMIZ1):c.-49-17111T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,064 control chromosomes in the GnomAD database, including 12,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12666 hom., cov: 32)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 10-79184473-T-G is Benign according to our data. Variant chr10-79184473-T-G is described in ClinVar as [Benign]. Clinvar id is 1281699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMIZ1	NM_020338.4	c.-49-17111T>G		intron_variant		ENST00000334512.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.-49-17111T>G		intron_variant		5	NM_020338.4	P1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60538 AN: 151946 Hom.: 12658 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.398 AC: 60555 AN: 152064 Hom.: 12666 Cov.: 32 AF XY: 0.400 AC XY: 29713 AN XY: 74350

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.389

Alfa AF: 0.440 Hom.: 7121

Bravo AF: 0.390

Asia WGS AF: 0.378 AC: 1315 AN: 3478

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

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 30181159) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.090
Dann	Benign	0.80

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: rs703977; hg19: chr10-80944230;