chr10-79081391-T-C

Variant names:

• chr10-79081391-T-C
• rs704010
• NM_020338.4:c.-337+12121T>C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_020338.4(ZMIZ1):c.-337+12121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene ZMIZ1 is a known oncogene (CancerMine: 5 oncogene citations). The variant allele was found at a cumulative frequency of 0.708 (AC=107,636) in the gnomAD database across 152,120 control chromosomes, including 39,367 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.905. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (39367 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 130 publications found

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]

ZMIZ1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.905 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_020338.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ZMIZ1 NM_020338.4	MANE Select	c.-337+12121T>C	intron	Intron 1 of 24	Prot: NP_065071.1 UniProt:

ZMIZ1 NM_020338.4

MANE Select

HGVSc / HGVSpc.-337+12121T>C

Exon rankIntron 1 of 24

intron

Prot: NP_065071.1UniProt: Q9ULJ6-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ZMIZ1 ENST00000334512.10	TSL:5MANE Select	c.-337+12121T>C	intron	Intron 1 of 24	Prot: ENSP00000334474.5 UniProt:
	ZMIZ1 ENST00000928256.1		c.-256+12121T>C	intron	Intron 1 of 23	Prot: ENSP00000598315.1 UniProt:
	ZMIZ1 ENST00000880201.1		c.-334+12121T>C	intron	Intron 1 of 24	Prot: ENSP00000550260.1 UniProt:

ZMIZ1 ENST00000334512.10

TSL:5MANE Select

HGVSc / HGVSpc.-337+12121T>C

Exon rankIntron 1 of 24

intron

Prot: ENSP00000334474.5UniProt: Q9ULJ6-1

ZMIZ1 ENST00000928256.1

HGVSc / HGVSpc.-256+12121T>C

Exon rankIntron 1 of 23

intron

Prot: ENSP00000598315.1UniProt: A0ACI8TGS8

ZMIZ1 ENST00000880201.1

HGVSc / HGVSpc.-334+12121T>C

Exon rankIntron 1 of 24

intron

Prot: ENSP00000550260.1UniProt: A0ACI8QNA3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.707	AC:107521	Hom:39308	AN:152000	Cov:33
GnomAD4 genome	AF: 0.708	AC:107636	Hom:39367	AN:152120	Cov:33
TOPMed (Bravo)	AF: 0.707	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.647	AC:390708	Hom:128785	AN:603442	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.659	AC:1543	Hom:500	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.691	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.513	AC:154	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.672	AC:2338	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.714	AC:5163	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.670	AC:118	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.722	AC:88643	Hom:32005	AN:122786	Cov:
Turkish Variome	AF: 0.641	AC:990	Hom:322	AN:1544	Cov:
UK10K	AF: 0.601	AC:4548	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.678	AC:6071	Hom:2062	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	3.5
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.64
GPN-Star LLR	N/A	4.1
GPN-Star score	N/A	-0.43
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.92
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.1

Showing 10 of 10 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs704010;

hg19: chr10-80841148;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar