Genetic Variant ZNFX1:p.Gln491Gln (chr20-49270339-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_021035.3(ZNFX1):c.1473A>G(p.Gln491Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,614,170 control chromosomes in the GnomAD database, including 722 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 0.015 ( 61 hom., cov: 32)

Exomes 𝑓: 0.021 ( 661 hom. )

Consequence

ZNFX1
NM_021035.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0110

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 91 and hyperinflammation
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ZNFX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP7

Synonymous conserved (PhyloP=0.011 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNFX1	NM_021035.3 link	c.1473A>G	p.Gln491Gln	synonymous_variant	Exon 3 of 14	ENST00000396105.6	NP_066363.1	Q9P2E3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNFX1	ENST00000396105.6 link	c.1473A>G	p.Gln491Gln	synonymous_variant	Exon 3 of 14	1	NM_021035.3	ENSP00000379412.1		Q9P2E3-1

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2323

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.0611

Gnomad SAS

AF:

0.0715

Gnomad FIN

AF:

0.00838

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.0249

AC:

6229

AN:

250624

AF XY:

0.0257

show subpopulations

Gnomad AFR exome

AF:

0.00327

Gnomad AMR exome

AF:

0.0354

Gnomad ASJ exome

AF:

0.00627

Gnomad EAS exome

AF:

0.0496

Gnomad FIN exome

AF:

0.00971

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.0213

GnomAD4 exome

AF:

0.0207

AC:

30262

AN:

1461816

Hom.:

661

Cov.:

AF XY:

0.0217

AC XY:

15778

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.00293

AC:

AN:

33480

American (AMR)

AF:

0.0345

AC:

1542

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00639

AC:

167

AN:

26136

East Asian (EAS)

AF:

0.0913

AC:

3626

AN:

39698

South Asian (SAS)

AF:

0.0632

AC:

5453

AN:

86258

European-Finnish (FIN)

AF:

0.0100

AC:

536

AN:

53374

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0157

AC:

17511

AN:

1111984

Other (OTH)

AF:

0.0213

AC:

1285

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1851

3702

5553

7404

9255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

754

1508

2262

3016

3770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0153

AC:

2329

AN:

152354

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1212

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00284

AC:

118

AN:

41590

American (AMR)

AF:

0.0226

AC:

346

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.0612

AC:

318

AN:

5192

South Asian (SAS)

AF:

0.0710

AC:

343

AN:

4834

European-Finnish (FIN)

AF:

0.00838

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0149

AC:

1013

AN:

68020

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

114

228

343

457

571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0150

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.0890

AC:

309

AN:

3478

EpiCase

AF:

0.0138

EpiControl

AF:

0.0139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.6

(source)

DANN

Benign

0.66

PhyloP100

0.011

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over