rs1359511

Variant names:

• chr10-79230882-A-C
• rs1359511
• NM_020338.4:c.280+14608A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-79230882-A-C
• chr10-79230882-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020338.4(ZMIZ1):​c.280+14608A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,172 control chromosomes in the GnomAD database, including 9,741 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 0.35 (9741 hom., cov: 33)
• Consequence: ZMIZ1 NM_020338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 1 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMIZ1	NM_020338.4	c.280+14608A>C		intron_variant	Intron 7 of 24	ENST00000334512.10	NP_065071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMIZ1	ENST00000334512.10	c.280+14608A>C		intron_variant	Intron 7 of 24	5	NM_020338.4	ENSP00000334474.5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53544 AN: 152054 Hom.: 9734 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.352 AC: 53583 AN: 152172 Hom.: 9741 Cov.: 33 AF XY: 0.349 AC XY: 25958 AN XY: 74390

African (AFR) AF: 0.304 AC: 12642 AN: 41524

American (AMR) AF: 0.353 AC: 5396 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1189 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5164

South Asian (SAS) AF: 0.275 AC: 1327 AN: 4824

European-Finnish (FIN) AF: 0.344 AC: 3647 AN: 10598

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27171 AN: 67974

Other (OTH) AF: 0.348 AC: 737 AN: 2116

Alfa AF: 0.251 Hom.: 729

Bravo AF: 0.354

Asia WGS AF: 0.267 AC: 929 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.77
PhyloP100		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1359511; hg19: chr10-80990639;