Genetic Variant ZNF341:p.Glu10Asp (chr20-33732051-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001282933.2(ZNF341):c.30G>T(p.Glu10Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000871 in 1,148,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E10Q) 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, splice_region

Scores

Splicing: ADA: 0.6978

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

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:

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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=0.09911981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF341	NM_001282933.2 link	c.30G>T	p.Glu10Asp	missense_variant, splice_region_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.30G>T	p.Glu10Asp	missense_variant, splice_region_variant	Exon 1 of 15	1	NM_001282933.2	ENSP00000364346.1		Q9BYN7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.71e-7

AC:

AN:

1148266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

553262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23166

American (AMR)

AF:

0.00

AC:

AN:

9390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15954

East Asian (EAS)

AF:

0.00

AC:

AN:

26854

South Asian (SAS)

AF:

0.00

AC:

AN:

39492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3618

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

950528

Other (OTH)

AF:

0.00

AC:

AN:

45734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.021

.;T

Eigen

Benign

-0.065

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.71

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PhyloP100

1.2

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.68

N;N

REVEL

Benign

0.056

Sift

Benign

0.13

T;T

Sift4G

Benign

0.097

T;T

Polyphen

0.97

D;B

Vest4

0.090

MutPred

0.15

Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.53

MPC

0.25

ClinPred

0.23

GERP RS

1.7

PromoterAI

0.093

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.14

gMVP

0.14

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.70

dbscSNV1_RF

Benign

0.49

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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20-33732051-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over