20-41182635-G-C

Variant names:

• chr20-41182635-G-C
• rs4297946
• NM_001384317.1:c.*2556C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 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=-0.91).
• 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 rank	MANE	Protein	UniProt
ZHX3	NM_001384317.1	c.*2556C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000683867.1	NP_001371246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZHX3	ENST00000683867.1	c.*2556C>G		3_prime_UTR_variant	Exon 4 of 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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.571 AC: 40 AN: 70

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.772 AC: 32038 AN: 41516

American (AMR) AF: 0.535 AC: 8184 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1564 AN: 3472

East Asian (EAS) AF: 0.819 AC: 4242 AN: 5178

South Asian (SAS) AF: 0.481 AC: 2318 AN: 4816

European-Finnish (FIN) AF: 0.536 AC: 5664 AN: 10566

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31581 AN: 67982

Other (OTH) AF: 0.545 AC: 1150 AN: 2112

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
PhyloP100		-0.37
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: rs4297946; hg19: chr20-39811275;