10-79195310-C-T

Position:

• chr10-79195310-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.-49-6274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,078 control chromosomes in the GnomAD database, including 13,669 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 0.42 (13669 hom., cov: 34)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.-49-6274C>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.-49-6274C>T		intron_variant		5	NM_020338.4	ENSP00000334474	P1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63982 AN: 151960 Hom.: 13660 Cov.: 34

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.421 AC: 64017 AN: 152078 Hom.: 13669 Cov.: 34 AF XY: 0.419 AC XY: 31127 AN XY: 74356

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.416

Alfa AF: 0.440 Hom.: 28132

Bravo AF: 0.416

Asia WGS AF: 0.306 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.70

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: rs703965; hg19: chr10-80955067;