10-79309656-A-G

Variant names:

• chr10-79309656-A-G
• rs942789
• NM_020338.4:c.2836-1268A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020338.4(ZMIZ1):​c.2836-1268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,220 control chromosomes in the GnomAD database, including 47,363 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 0.78 (47363 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.2836-1268A>G		intron_variant	Intron 23 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.2836-1268A>G		intron_variant	Intron 23 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119203 AN: 152102 Hom.: 47313 Cov.: 33

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.784 AC: 119308 AN: 152220 Hom.: 47363 Cov.: 33 AF XY: 0.779 AC XY: 57940 AN XY: 74412

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.808

Alfa AF: 0.741 Hom.: 23323

Bravo AF: 0.801

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.78

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: rs942789; hg19: chr10-81069413;