7-44757383-C-T

Variant names:

• chr7-44757383-C-T
• rs1456868032
• NM_031449.4:c.374C>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.374C>T​(p.Ala125Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZMIZ2 NM_031449.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18
• 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=0.16379398).

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.374C>T	p.Ala125Val	missense	Exon 5 of 19	NP_113637.3
	ZMIZ2	NM_174929.2		c.374C>T	p.Ala125Val	missense	Exon 4 of 17	NP_777589.2	Q8NF64-2
	ZMIZ2	NM_001300959.2		c.278C>T	p.Ala93Val	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.374C>T	p.Ala125Val	missense	Exon 5 of 19	ENSP00000311778.4	Q8NF64-1
	ZMIZ2	ENST00000441627.5	TSL:1	c.374C>T	p.Ala125Val	missense	Exon 4 of 18	ENSP00000414723.1	Q8NF64-1
	ZMIZ2	ENST00000413916.5	TSL:1	c.278C>T	p.Ala93Val	missense	Exon 5 of 18	ENSP00000409648.1	Q8NF64-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 233004 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447242 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 720302

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.0000225 AC: 1 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110806

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome Cov.: 33

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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.044
Sift	Benign	0.056	T
Sift4G	Benign	0.21	T
Polyphen		0.0020	B
Vest4		0.40
MutPred		0.37		Loss of disorder (P = 0.0676)
MVP		0.093
MPC		0.42
ClinPred		0.48	T
GERP RS		4.6
Varity_R		0.13
gMVP		0.56
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1456868032; hg19: chr7-44796982;