8-122951761-C-T

Variant names:

• chr8-122951761-C-T
• rs1273308504
• NM_014943.5:c.251C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014943.5(ZHX2):​c.251C>T​(p.Pro84Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P84R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZHX2 NM_014943.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZHX2	NM_014943.5	c.251C>T	p.Pro84Leu	missense_variant	Exon 3 of 4	ENST00000314393.6	NP_055758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZHX2	ENST00000314393.6	c.251C>T	p.Pro84Leu	missense_variant	Exon 3 of 4	1	NM_014943.5	ENSP00000314709.4
ZHX2	ENST00000534247.1	c.251C>T	p.Pro84Leu	missense_variant	Exon 2 of 2	3		ENSP00000452720.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		1.0	D;.
Vest4		0.80
MutPred		0.31		Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP		0.77
MPC		0.94
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.30
gMVP		0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1273308504; hg19: chr8-123964001;