NM_014943.5:c.512G>A

Variant names:

• chr8-122952022-G-A
• NM_014943.5:c.512G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014943.5(ZHX2):​c.512G>A​(p.Gly171Glu) 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. 16/22 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. G171R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZHX2 NM_014943.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.566
• Publications: 0 publications found

Genes affected

ZHX2 (HGNC:18513): (zinc fingers and homeoboxes 2) The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 2 of this gene family. In addition to forming homodimers, this protein heterodimerizes with member 1 of the zinc fingers and homeoboxes family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034443736).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014943.5. 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
	ZHX2	NM_014943.5	MANE Select	c.512G>A	p.Gly171Glu	missense	Exon 3 of 4	NP_055758.1	Q9Y6X8
	ZHX2	NM_001362797.2		c.512G>A	p.Gly171Glu	missense	Exon 4 of 5	NP_001349726.1	Q9Y6X8
	ZHX2	NM_001412796.1		c.512G>A	p.Gly171Glu	missense	Exon 4 of 5	NP_001399725.1	Q9Y6X8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZHX2	ENST00000314393.6	TSL:1 MANE Select	c.512G>A	p.Gly171Glu	missense	Exon 3 of 4	ENSP00000314709.4	Q9Y6X8
	ZHX2	ENST00000892386.1		c.512G>A	p.Gly171Glu	missense	Exon 4 of 5	ENSP00000562445.1
	ZHX2	ENST00000892387.1		c.512G>A	p.Gly171Glu	missense	Exon 4 of 5	ENSP00000562446.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.084
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.68
DANN	Benign	0.69
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.57
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.025
Sift	Benign	0.48	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.15		Gain of solvent accessibility (P = 0.0246)
MVP		0.17
MPC		0.34
ClinPred		0.043	T
GERP RS		2.1
Varity_R		0.020
gMVP		0.25
Mutation Taster		=99/1	polymorphism

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

hg19: chr8-123964262;