20-49245566-A-G

Variant names:

• chr20-49245566-A-G
• rs238206
• ENST00000371754.8:c.3313-3643T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000371754.8(ZNFX1):​c.3313-3643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,834 control chromosomes in the GnomAD database, including 34,841 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 0.67 (34841 hom., cov: 30)
• Consequence: ZNFX1 ENST00000371754.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812
• Publications: 5 publications found

Genes affected

ZNFX1 (HGNC:29271): (zinc finger NFX1-type containing 1) Enables RNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA. Predicted to be part of nuclear RNA-directed RNA polymerase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNFX1 Gene-Disease associations (from GenCC):

• immunodeficiency 91 and hyperinflammation

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNFX1	ENST00000371754.8	c.3313-3643T>C		intron_variant	Intron 13 of 14	1		ENSP00000360819.4

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101412 AN: 151716 Hom.: 34834 Cov.: 30

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.668 AC: 101443 AN: 151834 Hom.: 34841 Cov.: 30 AF XY: 0.664 AC XY: 49270 AN XY: 74178

African (AFR) AF: 0.529 AC: 21894 AN: 41364

American (AMR) AF: 0.605 AC: 9236 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2736 AN: 3468

East Asian (EAS) AF: 0.505 AC: 2603 AN: 5156

South Asian (SAS) AF: 0.552 AC: 2648 AN: 4796

European-Finnish (FIN) AF: 0.792 AC: 8339 AN: 10532

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51667 AN: 67952

Other (OTH) AF: 0.668 AC: 1405 AN: 2104

Alfa AF: 0.660 Hom.: 2155

Bravo AF: 0.647

Asia WGS AF: 0.554 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs238206; hg19: chr20-47862103;