20-41185409-A-AG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001384317.1(ZHX3):c.2861-209_2861-208insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,154 control chromosomes in the GnomAD database, including 1,165 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1165 hom., cov: 31)
• Consequence: ZHX3 NM_001384317.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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 -10 ACMG points.

• BP6: Variant 20-41185409-A-AG is Benign according to our data. Variant chr20-41185409-A-AG is described in ClinVar as [Benign]. Clinvar id is 1285731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZHX3	NM_001384317.1	c.2861-209_2861-208insC		intron_variant		ENST00000683867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZHX3	ENST00000683867.1	c.2861-209_2861-208insC		intron_variant			NM_001384317.1	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15471 AN: 152036 Hom.: 1163 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.0506

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.102 AC: 15483 AN: 152154 Hom.: 1165 Cov.: 31 AF XY: 0.101 AC XY: 7510 AN XY: 74392

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0648

Gnomad4 ASJ AF: 0.0616

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.0920

Gnomad4 NFE AF: 0.0580

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0765 Hom.: 79

Bravo AF: 0.104

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs55792704; hg19: chr20-39814049;