rs368945563

Positions:

chr20-33791116-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6_ModerateBS1

The NM_001282933.2(ZNF341):c.2164C>T(p.Arg722Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,346 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R722H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

ZNF341
NM_001282933.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.45

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 links:

ZNF341-AS1 (HGNC:50736): (ZNF341 antisense RNA 1)

ZNF341-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19964933).

BP6

Variant 20-33791116-C-T is Benign according to our data. Variant chr20-33791116-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 207894.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000394 (6/152342) while in subpopulation AMR AF= 0.000327 (5/15308). AF 95% confidence interval is 0.000129. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF341	NM_001282933.2 linkuse as main transcript	c.2164C>T	p.Arg722Cys	missense_variant	15/15	ENST00000375200.6
ZNF341-AS1	NR_110623.1 linkuse as main transcript	n.242-3339G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF341	ENST00000375200.6 linkuse as main transcript	c.2164C>T	p.Arg722Cys	missense_variant	15/15	1	NM_001282933.2	P4	Q9BYN7-1
ZNF341-AS1	ENST00000443171.6 linkuse as main transcript	n.252-3339G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000232

AC:

AN:

249488

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000595

AC:

AN:

1461004

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000264

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 24, 2023

- -

Long QT syndrome

Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.61

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-4.0

D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.038

D;D

Polyphen

1.0

D;D

Vest4

0.93

MutPred

0.39

.;Loss of MoRF binding (P = 0.0171);

MVP

0.79

MPC

1.1

ClinPred

0.25

GERP RS

5.0

Varity_R

0.23

gMVP

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over