20-41184366-C-T

Position:

• chr20-41184366-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384317.1(ZHX3):​c.*825G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 153,192 control chromosomes in the GnomAD database, including 746 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 0.042 (745 hom., cov: 33)
  • Exomes 𝑓: 0.022 (1 hom.)
• Consequence: ZHX3 NM_001384317.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941

Genes affected

ZHX3 (HGNC:15935): (zinc fingers and homeoboxes 3) This gene encodes a member of the zinc fingers and homeoboxes (ZHX) gene family. The encoded protein contains two C2H2-type zinc fingers and five homeodomains and forms a dimer with itself or with zinc fingers and homeoboxes family member 1. In the nucleus, the dimerized protein interacts with the A subunit of the ubiquitous transcription factor nuclear factor-Y and may function as a transcriptional repressor. [provided by RefSeq, Jul 2008]

PLCG1 (HGNC:9065): (phospholipase C gamma 1) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RasGRP1 to translocate to the Golgi, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZHX3	NM_001384317.1	c.*825G>A		3_prime_UTR_variant	4/4	ENST00000683867.1	NP_001371246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZHX3	ENST00000683867.1	c.*825G>A		3_prime_UTR_variant	4/4		NM_001384317.1	ENSP00000506788	P1

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6301 AN: 151584 Hom.: 747 Cov.: 33

Gnomad AFR AF: 0.00950

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.00694

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0394

GnomAD4 exome AF: 0.0221 AC: 33 AN: 1490 Hom.: 1 Cov.: 0 AF XY: 0.0187 AC XY: 14 AN XY: 748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.00924

Gnomad4 OTH exome AF: 0.0278

GnomAD4 genome AF: 0.0416 AC: 6306 AN: 151702 Hom.: 745 Cov.: 33 AF XY: 0.0467 AC XY: 3465 AN XY: 74128

Gnomad4 AFR AF: 0.00959

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.00694

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0390

Alfa AF: 0.0390 Hom.: 178

Bravo AF: 0.0493

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.51

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: rs2076147; hg19: chr20-39813006;