20-33732049-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001282933.2(ZNF341):c.28G>C(p.Glu10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000866 in 1,154,270 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. E10E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

ZNF341
NM_001282933.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11602503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF341	NM_001282933.2 link	c.28G>C	p.Glu10Gln	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.28G>C	p.Glu10Gln	missense_variant	Exon 1 of 15	1	NM_001282933.2	ENSP00000364346.1		Q9BYN7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

18012

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

8.66e-7

AC:

AN:

1154270

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

556900

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23232

American (AMR)

AF:

0.00

AC:

AN:

9666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16124

East Asian (EAS)

AF:

0.0000372

AC:

AN:

26894

South Asian (SAS)

AF:

0.00

AC:

AN:

41082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3658

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

953684

Other (OTH)

AF:

0.00

AC:

AN:

46016

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.28G>C (p.E10Q) alteration is located in exon 1 (coding exon 1) of the ZNF341 gene. This alteration results from a G to C substitution at nucleotide position 28, causing the glutamic acid (E) at amino acid position 10 to be replaced by a glutamine (Q). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

.;T

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.059

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PhyloP100

3.1

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.073

Sift

Benign

0.066

T;D

Sift4G

Uncertain

0.050

T;D

Polyphen

0.99

D;B

Vest4

0.11

MutPred

0.14

Loss of catalytic residue at N14 (P = 0.187);Loss of catalytic residue at N14 (P = 0.187);

MVP

0.50

MPC

0.31

ClinPred

0.45

GERP RS

1.7

PromoterAI

0.099

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.29

Mutation Taster

=85/15

polymorphism

(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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20-33732049-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over