20-41185088-CGG-TAA

Variant names:

• chr20-41185088-CGG-TAA
• ENST00000544979.6:c.2746_2748delCCGinsTTA
• ZHX3 p.Pro916Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001384324.1(ZHX3):​c.2746_2748delCCGinsTTA​(p.Pro916Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZHX3 NM_001384324.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 0 publications found

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]

PLCG1 Gene-Disease associations (from GenCC):

• immune dysregulation, autoimmunity, and autoinflammation

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384324.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZHX3	NM_001384317.1	MANE Select	c.*101_*103delCCGinsTTA		3_prime_UTR	Exon 4 of 4	NP_001371246.1	Q9H4I2-1
	ZHX3	NM_001384324.1		c.2746_2748delCCGinsTTA	p.Pro916Leu	missense	N/A	NP_001371253.1	Q9H4I2-2
	ZHX3	NM_001384325.1		c.*161_*163delCCGinsTTA		3_prime_UTR	Exon 5 of 5	NP_001371254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZHX3	ENST00000544979.6	TSL:1	c.2746_2748delCCGinsTTA	p.Pro916Leu	missense	N/A	ENSP00000443783.2	Q9H4I2-2
	ZHX3	ENST00000683867.1	MANE Select	c.*101_*103delCCGinsTTA		3_prime_UTR	Exon 4 of 4	ENSP00000506788.1	Q9H4I2-1
	ZHX3	ENST00000559234.5	TSL:1	c.*101_*103delCCGinsTTA		3_prime_UTR	Exon 4 of 4	ENSP00000452965.1	Q9H4I2-1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-39813728;