Variant chr19-8511820-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001146175.2(ZNF414):c.671C>T(p.Pro224Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,248,558 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ZNF414
NM_001146175.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.177

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07638338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF414	NM_001146175.2 linkuse as main transcript	c.671C>T	p.Pro224Leu	missense_variant	5/8	ENST00000393927.9	NP_001139647.1	Q96IQ9-2
ZNF414	NM_032370.3 linkuse as main transcript	c.671C>T	p.Pro224Leu	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.671C>T	p.Pro224Leu	missense_variant	5/8	1	NM_001146175.2	ENSP00000377504.3		Q96IQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1248558

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

605526

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000695

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:

0.0000147

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.671C>T (p.P224L) alteration is located in exon 5 (coding exon 5) of the ZNF414 gene. This alteration results from a C to T substitution at nucleotide position 671, causing the proline (P) at amino acid position 224 to be replaced by a leucine (L). 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

Benign

0.082

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.9

DANN

Benign

0.95

DEOGEN2

Benign

0.0036

.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.029

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.32

.;B

Vest4

0.13

MutPred

0.20

Loss of catalytic residue at P223 (P = 0.0165);Loss of catalytic residue at P223 (P = 0.0165);

MVP

0.21

MPC

0.29

ClinPred

0.21

GERP RS

1.1

Varity_R

0.039

gMVP

0.47

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

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