20-41182635-G-C

Position:

• chr20-41182635-G-C

Variant summary

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

The NM_001384317.1(ZHX3):​c.*2556C>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 0.574 in 152,212 control chromosomes in the GnomAD database, including 26,513 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 0.57 (26497 hom., cov: 33)
  • Exomes 𝑓: 0.58 (16 hom.)
• Consequence: ZHX3 NM_001384317.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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:):

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZHX3	NM_001384317.1	c.*2556C>G		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	c.*2556C>G		3_prime_UTR_variant	4/4		NM_001384317.1	ENSP00000506788.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87175 AN: 152014 Hom.: 26455 Cov.: 33

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.542

GnomAD4 exome AF: 0.577 AC: 45 AN: 78 Hom.: 16 Cov.: 0 AF XY: 0.617 AC XY: 37 AN XY: 60

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.574 AC: 87285 AN: 152134 Hom.: 26497 Cov.: 33 AF XY: 0.575 AC XY: 42741 AN XY: 74350

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.545

Alfa AF: 0.404 Hom.: 1226

Bravo AF: 0.585

Asia WGS AF: 0.642 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.54

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: rs4297946; hg19: chr20-39811275;