20-41184366-C-T

Variant names:

• chr20-41184366-C-T
• rs2076147
• NM_001384317.1:c.*825G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384317.1. 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.*825G>A		3_prime_UTR	Exon 4 of 4	NP_001371246.1
	ZHX3	NM_001384324.1		c.*560G>A		3_prime_UTR	Exon 5 of 5	NP_001371253.1
	ZHX3	NM_001384325.1		c.*885G>A		3_prime_UTR	Exon 5 of 5	NP_001371254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZHX3	ENST00000683867.1	MANE Select	c.*825G>A		3_prime_UTR	Exon 4 of 4	ENSP00000506788.1
	ZHX3	ENST00000559234.5	TSL:1	c.*825G>A		3_prime_UTR	Exon 4 of 4	ENSP00000452965.1
	ZHX3	ENST00000421422.1	TSL:1	c.*885G>A		3_prime_UTR	Exon 3 of 3	ENSP00000405421.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.103 AC: 19 AN: 184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 52

European-Finnish (FIN) AF: 0.0625 AC: 1 AN: 16

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00924 AC: 11 AN: 1190

Other (OTH) AF: 0.0278 AC: 1 AN: 36

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

African (AFR) AF: 0.00959 AC: 398 AN: 41504

American (AMR) AF: 0.106 AC: 1609 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00694 AC: 24 AN: 3456

East Asian (EAS) AF: 0.477 AC: 2466 AN: 5172

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4818

European-Finnish (FIN) AF: 0.0533 AC: 563 AN: 10572

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 972 AN: 67650

Other (OTH) AF: 0.0390 AC: 82 AN: 2104

Alfa AF: 0.0368 Hom.: 181

Bravo AF: 0.0493

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.94
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: rs2076147; hg19: chr20-39813006;