Variant 20-49247506-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_021035.3(ZNFX1):c.5518G>A(p.Gly1840Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNFX1
NM_021035.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZNFX1. . Gene score misZ 2.5616 (greater than the threshold 3.09). Trascript score misZ 4.0768 (greater than threshold 3.09). GenCC has associacion of gene with immunodeficiency 91 and hyperinflammation.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNFX1	NM_021035.3 link	c.5518G>A	p.Gly1840Ser	missense_variant	14/14	ENST00000396105.6	NP_066363.1	Q9P2E3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNFX1	ENST00000396105.6 link	c.5518G>A	p.Gly1840Ser	missense_variant	14/14	1	NM_021035.3	ENSP00000379412.1	Q9P2E3-1
ZNFX1	ENST00000371754.8 link	c.3312+4021G>A		intron_variant		1		ENSP00000360819.4	Q5JXR6
ZNFX1	ENST00000371752.5 link	c.5518G>A	p.Gly1840Ser	missense_variant	14/14	5		ENSP00000360817.1	Q9P2E3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.5518G>A (p.G1840S) alteration is located in exon 14 (coding exon 13) of the ZNFX1 gene. This alteration results from a G to A substitution at nucleotide position 5518, causing the glycine (G) at amino acid position 1840 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.87

.;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.023

D;D

Polyphen

1.0

D;D

Vest4

0.49

MutPred

0.49

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.56

MPC

1.1

ClinPred

0.99

GERP RS

5.1

Varity_R

0.34

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over