Variant 19-8511890-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 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

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:

ZNF414 (HGNC:):

ZNF414 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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/exons	MANE	Protein	UniProt
ZNF414	NM_001146175.2 linkuse as main transcript	c.601C>A	p.His201Asn	missense_variant	5/8	ENST00000393927.9	NP_001139647.1	Q96IQ9-2
ZNF414	NM_032370.3 linkuse as main transcript	c.601C>A	p.His201Asn	missense_variant	5/6		NP_115746.2	Q96IQ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF414	ENST00000393927.9 linkuse as main transcript	c.601C>A	p.His201Asn	missense_variant	5/8	1	NM_001146175.2	ENSP00000377504.3		Q96IQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.93e-7

AC:

AN:

1260526

Hom.:

Cov.:

AF XY:

0.00000163

AC XY:

AN XY:

612634

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.77e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2022

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

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

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

Varity_R

0.076

gMVP

0.21

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

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