Variant 19-57491527-G-T 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_024691.4(ZNF419):c.129G>T(p.Leu43Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF419
NM_024691.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.654

Variant links:

Genes affected

ZNF419 (HGNC:20648): (zinc finger protein 419) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF419 links:

ZNF419 (HGNC:):

ZNF419 links:

Genome browser will be placed here

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=0.23773012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF419	NM_024691.4 linkuse as main transcript	c.129G>T	p.Leu43Phe	missense_variant	3/5	ENST00000221735.12	NP_078967.3	Q96HQ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF419	ENST00000221735.12 linkuse as main transcript	c.129G>T	p.Leu43Phe	missense_variant	3/5	1	NM_024691.4	ENSP00000221735.7		Q96HQ0-1
ENSG00000268107	ENST00000601674.6 linkuse as main transcript	n.90G>T		non_coding_transcript_exon_variant	2/6	2		ENSP00000471625.1		M0R143

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251490

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Mar 29, 2024

The c.132G>T (p.L44F) alteration is located in exon 3 (coding exon 3) of the ZNF419 gene. This alteration results from a G to T substitution at nucleotide position 132, causing the leucine (L) at amino acid position 44 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

.;.;.;.;.;.;.;.;.;.;.;T;.;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.24

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.2

.;.;.;.;.;.;.;.;.;.;.;M;.;.

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0090

D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.056

T;T;T;T;T;T;T;D;T;D;D;T;T;D

Polyphen

0.037, 1.0

.;.;.;.;.;.;.;B;.;.;.;D;.;.

Vest4

0.33

MutPred

0.67

.;.;.;.;.;.;.;.;Loss of stability (P = 0.0601);.;.;Loss of stability (P = 0.0601);.;Loss of stability (P = 0.0601);

MVP

0.088

MPC

0.17

ClinPred

0.53

GERP RS

-0.90

Varity_R

0.12

gMVP

0.20

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