8-122928345-T-G

Variant names:

• chr8-122928345-T-G
• rs9792311
• NM_014943.5:c.-219-22947T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014943.5(ZHX2):​c.-219-22947T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,108 control chromosomes in the GnomAD database, including 7,212 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 0.30 (7212 hom., cov: 32)
• Consequence: ZHX2 NM_014943.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZHX2	NM_014943.5	c.-219-22947T>G		intron_variant	Intron 2 of 3	ENST00000314393.6	NP_055758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZHX2	ENST00000314393.6	c.-219-22947T>G		intron_variant	Intron 2 of 3	1	NM_014943.5	ENSP00000314709.4
ZHX2	ENST00000534247.1	c.-219-22947T>G		intron_variant	Intron 1 of 1	3		ENSP00000452720.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45186 AN: 151988 Hom.: 7195 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45242 AN: 152108 Hom.: 7212 Cov.: 32 AF XY: 0.294 AC XY: 21901 AN XY: 74370

African (AFR) AF: 0.422 AC: 17501 AN: 41456

American (AMR) AF: 0.289 AC: 4416 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1645 AN: 5170

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4828

European-Finnish (FIN) AF: 0.202 AC: 2133 AN: 10582

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16137 AN: 68000

Other (OTH) AF: 0.310 AC: 655 AN: 2112

Alfa AF: 0.235 Hom.: 2252

Bravo AF: 0.312

Asia WGS AF: 0.283 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		-0.022
Mutation Taster		=100/0	polymorphism (auto)

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: rs9792311; hg19: chr8-123940585;