chr7-44757391-C-G

Variant names:

• chr7-44757391-C-G
• rs201911821
• NM_031449.4:c.382C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_031449.4(ZMIZ2):​c.382C>G​(p.Pro128Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000567 in 1,600,798 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P128L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (2 hom.)
• Consequence: ZMIZ2 NM_031449.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• Publications: 3 publications found

Genes affected

ZMIZ2 (HGNC:22229): (zinc finger MIZ-type containing 2) ZMIZ2 and ZMIZ1 (MIM 607159) are members of a PIAS (see MIM 603566)-like family of proteins that interact with nuclear hormone receptors. ZMIZ2 interacts with androgen receptor (AR; MIM 313700) and enhances AR-mediated transcription (Huang et al., 2005 [PubMed 16051670]).[supplied by OMIM, May 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06146869).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031449.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ2	NM_031449.4	MANE Select	c.382C>G	p.Pro128Ala	missense	Exon 5 of 19	NP_113637.3
	ZMIZ2	NM_174929.2		c.382C>G	p.Pro128Ala	missense	Exon 4 of 17	NP_777589.2	Q8NF64-2
	ZMIZ2	NM_001300959.2		c.286C>G	p.Pro96Ala	missense	Exon 5 of 18	NP_001287888.1	Q8NF64-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMIZ2	ENST00000309315.9	TSL:2 MANE Select	c.382C>G	p.Pro128Ala	missense	Exon 5 of 19	ENSP00000311778.4	Q8NF64-1
	ZMIZ2	ENST00000441627.5	TSL:1	c.382C>G	p.Pro128Ala	missense	Exon 4 of 18	ENSP00000414723.1	Q8NF64-1
	ZMIZ2	ENST00000413916.5	TSL:1	c.286C>G	p.Pro96Ala	missense	Exon 5 of 18	ENSP00000409648.1	Q8NF64-3

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000252 AC: 59 AN: 234078 AF XY: 0.000209

Gnomad AFR exome AF: 0.0000687

Gnomad AMR exome AF: 0.000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000722

Gnomad NFE exome AF: 0.000429

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000594 AC: 861 AN: 1448604 Hom.: 2 Cov.: 33 AF XY: 0.000583 AC XY: 420 AN XY: 721006

African (AFR) AF: 0.0000898 AC: 3 AN: 33414

American (AMR) AF: 0.000314 AC: 14 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.000120 AC: 5 AN: 41532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.000736 AC: 818 AN: 1111120

Other (OTH) AF: 0.000349 AC: 21 AN: 60240

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74354

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68024

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000634 Hom.: 0

Bravo AF: 0.000272

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000487 AC: 4

ExAC AF: 0.000166 AC: 20

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.75
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.037
Sift	Benign	0.098	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.32
MVP		0.11
MPC		0.37
ClinPred		0.043	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.58
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201911821; hg19: chr7-44796990; COSMIC: COSV99037291; COSMIC: COSV99037291;