8-122974409-A-G

Position:

• chr8-122974409-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014943.5(ZHX2):​c.*1172A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,570 control chromosomes in the GnomAD database, including 20,862 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (20850 hom., cov: 29)
  • Exomes 𝑓: 0.35 (12 hom.)
• Consequence: ZHX2 NM_014943.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZHX2	NM_014943.5	c.*1172A>G		3_prime_UTR_variant	4/4	ENST00000314393.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZHX2	ENST00000314393.6	c.*1172A>G		3_prime_UTR_variant	4/4	1	NM_014943.5	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77225 AN: 151152 Hom.: 20809 Cov.: 29

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.350 AC: 105 AN: 300 Hom.: 12 Cov.: 0 AF XY: 0.337 AC XY: 62 AN XY: 184

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.511 AC: 77325 AN: 151270 Hom.: 20850 Cov.: 29 AF XY: 0.507 AC XY: 37429 AN XY: 73848

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.518

Alfa AF: 0.463 Hom.: 16572

Bravo AF: 0.521

Asia WGS AF: 0.439 AC: 1528 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2833; hg19: chr8-123986649; COSMIC: COSV58713812; COSMIC: COSV58713812;