Variant chr20-49247452-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The ENST00000396105.6(ZNFX1):c.5572G>A(p.Gly1858Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNFX1
ENST00000396105.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.672

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 Likely_benign. Variant got -1 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.07349515).

BP6

Variant 20-49247452-C-T is Benign according to our data. Variant chr20-49247452-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3199090.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNFX1	NM_021035.3 linkuse as main transcript	c.5572G>A	p.Gly1858Ser	missense_variant	14/14	ENST00000396105.6	NP_066363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNFX1	ENST00000396105.6 linkuse as main transcript	c.5572G>A	p.Gly1858Ser	missense_variant	14/14	1	NM_021035.3	ENSP00000379412	P1	Q9P2E3-1
ZNFX1	ENST00000371754.8 linkuse as main transcript	c.3312+4075G>A		intron_variant		1		ENSP00000360819
ZNFX1	ENST00000371752.5 linkuse as main transcript	c.5572G>A	p.Gly1858Ser	missense_variant	14/14	5		ENSP00000360817	P1	Q9P2E3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.39

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.073

T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.32

Sift

Benign

0.20

T;T

Sift4G

Uncertain

0.057

T;T

Polyphen

0.0020

B;B

Vest4

0.083

MutPred

0.41

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.21

MPC

0.39

ClinPred

0.058

GERP RS

-4.1

Varity_R

0.086

gMVP

0.47

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