10-79081024-C-G

Position:

• chr10-79081024-C-G

Variant summary

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

The NM_020338.4(ZMIZ1):​c.-337+11754C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,194 control chromosomes in the GnomAD database, including 1,407 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 0.13 (1407 hom., cov: 31)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.-337+11754C>G		intron_variant		ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.-337+11754C>G		intron_variant		5	NM_020338.4	ENSP00000334474	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19749 AN: 152076 Hom.: 1406 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.130 AC: 19750 AN: 152194 Hom.: 1407 Cov.: 31 AF XY: 0.131 AC XY: 9774 AN XY: 74414

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.119

Alfa AF: 0.112 Hom.: 130

Bravo AF: 0.134

Asia WGS AF: 0.185 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.40

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: rs4980025; hg19: chr10-80840781;