NM_014943.5:c.359A>C

Variant names:

• chr8-122951869-A-C
• rs1813123429
• NM_014943.5:c.359A>C

Variant summary

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

The NM_014943.5(ZHX2):​c.359A>C​(p.Lys120Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ZHX2 NM_014943.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.90
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.359A>C	p.Lys120Thr	missense	Exon 3 of 4	NP_055758.1	Q9Y6X8
	ZHX2	NM_001362797.2		c.359A>C	p.Lys120Thr	missense	Exon 4 of 5	NP_001349726.1	Q9Y6X8
	ZHX2	NM_001412796.1		c.359A>C	p.Lys120Thr	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.359A>C	p.Lys120Thr	missense	Exon 3 of 4	ENSP00000314709.4	Q9Y6X8
	ZHX2	ENST00000892386.1		c.359A>C	p.Lys120Thr	missense	Exon 4 of 5	ENSP00000562445.1
	ZHX2	ENST00000892387.1		c.359A>C	p.Lys120Thr	missense	Exon 4 of 5	ENSP00000562446.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.9
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.40		Gain of sheet (P = 0.0125)
MVP		0.82
MPC		1.0
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.83
Mutation Taster		=78/22	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

dbSNP: rs1813123429; hg19: chr8-123964109;