Genetic Variant ZNF414:p.His201Asn (chr19-8511890-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001146175.2(ZNF414):c.601C>A(p.His201Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,260,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

ZNF414
NM_001146175.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01

Publications

0 publications found

Variant links:

Genes affected

ZNF414 (HGNC:20630): (zinc finger protein 414) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ZNF414 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12675178).

BP6

Variant 19-8511890-G-T is Benign according to our data. Variant chr19-8511890-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2307484.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF414	NM_001146175.2 link	c.601C>A	p.His201Asn	missense_variant	Exon 5 of 8	ENST00000393927.9	NP_001139647.1	Q96IQ9-2
ZNF414	NM_032370.3 link	c.601C>A	p.His201Asn	missense_variant	Exon 5 of 6		NP_115746.2	Q96IQ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF414	ENST00000393927.9 link	c.601C>A	p.His201Asn	missense_variant	Exon 5 of 8	1	NM_001146175.2	ENSP00000377504.3		Q96IQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000130

AC:

AN:

76956

AF XY:

0.0000230

show subpopulations

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:

0.0000229

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.93e-7

AC:

AN:

1260526

Hom.:

Cov.:

AF XY:

0.00000163

AC XY:

AN XY:

612634

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25702

American (AMR)

AF:

0.00

AC:

AN:

16954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17208

East Asian (EAS)

AF:

0.00

AC:

AN:

32324

South Asian (SAS)

AF:

0.00

AC:

AN:

55374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3866

European-Non Finnish (NFE)

AF:

9.77e-7

AC:

AN:

1023684

Other (OTH)

AF:

0.00

AC:

AN:

51798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

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.:

ExAC

AF:

0.0000270

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 15, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L

PhyloP100

1.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.13

Sift

Benign

0.19

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.98

.;D

Vest4

0.18

MutPred

0.15

Loss of phosphorylation at S204 (P = 0.1893);Loss of phosphorylation at S204 (P = 0.1893);

MVP

0.37

MPC

0.81

ClinPred

0.12

GERP RS

3.9

PromoterAI

-0.39

Neutral

(source)

Varity_R

0.076

gMVP

0.21

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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