chr7-44757915-C-T

Variant names:

• chr7-44757915-C-T
• NM_031449.4:c.620C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031449.4(ZMIZ2):​c.620C>T​(p.Pro207Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMIZ2 NM_031449.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08384484).

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.620C>T	p.Pro207Leu	missense	Exon 6 of 19	NP_113637.3
	ZMIZ2	NM_174929.2		c.620C>T	p.Pro207Leu	missense	Exon 5 of 17	NP_777589.2	Q8NF64-2
	ZMIZ2	NM_001300959.2		c.524C>T	p.Pro175Leu	missense	Exon 6 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.620C>T	p.Pro207Leu	missense	Exon 6 of 19	ENSP00000311778.4	Q8NF64-1
	ZMIZ2	ENST00000441627.5	TSL:1	c.620C>T	p.Pro207Leu	missense	Exon 5 of 18	ENSP00000414723.1	Q8NF64-1
	ZMIZ2	ENST00000413916.5	TSL:1	c.524C>T	p.Pro175Leu	missense	Exon 6 of 18	ENSP00000409648.1	Q8NF64-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Benign	0.73
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.052
Sift	Benign	0.035	D
Sift4G	Benign	0.16	T
Polyphen		0.81	P
Vest4		0.62
MutPred		0.25		Loss of loop (P = 0.0603)
MVP		0.043
MPC		0.52
ClinPred		0.23	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.58
Mutation Taster		=75/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr7-44797514;