20-33732041-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_001282933.2(ZNF341):c.20A>G(p.Glu7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,353,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E7E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

ZNF341
NM_001282933.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Publications

0 publications found

Variant links:

Genes affected

ZNF341 (HGNC:15992): (zinc finger protein 341) Enables DNA binding activity and DNA-binding transcription activator activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleus. Implicated in hyper IgE recurrent infection syndrome 3. [provided by Alliance of Genome Resources, Apr 2022]

ZNF341 Gene-Disease associations (from GenCC):

hyper-IgE recurrent infection syndrome 3, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ZNF341 links:

ENSG00000229188 (HGNC:):

ENSG00000229188 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08050436).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000238 (36/151178) while in subpopulation AMR AF = 0.00237 (36/15192). AF 95% confidence interval is 0.00176. There are 0 homozygotes in GnomAd4. There are 25 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF341	NM_001282933.2 link	c.20A>G	p.Glu7Gly	missense_variant	Exon 1 of 15	ENST00000375200.6	NP_001269862.1	Q9BYN7-1Q504V9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF341	ENST00000375200.6 link	c.20A>G	p.Glu7Gly	missense_variant	Exon 1 of 15	1	NM_001282933.2	ENSP00000364346.1		Q9BYN7-1

Frequencies

GnomAD3 genomes

AF:

0.000238

AC:

AN:

151178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00237

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000331

AC:

AN:

30186

AF XY:

0.0000584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000308

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.32e-7

AC:

AN:

1202246

Hom.:

Cov.:

AF XY:

0.00000171

AC XY:

AN XY:

585482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23942

American (AMR)

AF:

0.0000794

AC:

AN:

12596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17840

East Asian (EAS)

AF:

0.00

AC:

AN:

27228

South Asian (SAS)

AF:

0.00

AC:

AN:

52220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3970

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

979354

Other (OTH)

AF:

0.00

AC:

AN:

48002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000238

AC:

AN:

151178

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

AN XY:

73806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41176

American (AMR)

AF:

0.00237

AC:

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67736

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000144

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZNF341-related disorder

Uncertain:1

Jan 17, 2023

PreventionGenetics, part of Exact Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The ZNF341 c.20A>G variant is predicted to result in the amino acid substitution p.Glu7Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.031% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-32319847-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.74

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PhyloP100

2.3

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.53

P;B

Vest4

0.099

MutPred

0.21

Loss of solvent accessibility (P = 0.0703);Loss of solvent accessibility (P = 0.0703);

MVP

0.63

MPC

0.34

ClinPred

0.15

GERP RS

1.5

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.10

gMVP

0.41

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over