Variant chr19-56574484-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001001668.4(ZNF470):c.151G>A(p.Val51Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

ZNF470
NM_001001668.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

ZNF470 (HGNC:22220): (zinc finger protein 470) 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. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ZNF470 links:

ZNF470 (HGNC:):

ZNF470 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF470	NM_001001668.4 linkuse as main transcript	c.151G>A	p.Val51Met	missense_variant	4/6	ENST00000330619.13	NP_001001668.3	Q6ECI4-1
ZNF470	XM_047438805.1 linkuse as main transcript	c.-3G>A		5_prime_UTR_premature_start_codon_gain_variant	3/5		XP_047294761.1
ZNF470	XM_047438804.1 linkuse as main transcript	c.151G>A	p.Val51Met	missense_variant	5/7		XP_047294760.1
ZNF470	XM_047438805.1 linkuse as main transcript	c.-3G>A		5_prime_UTR_variant	3/5		XP_047294761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF470	ENST00000330619.13 linkuse as main transcript	c.151G>A	p.Val51Met	missense_variant	4/6	1	NM_001001668.4	ENSP00000333223.7	Q6ECI4-1
ZNF470	ENST00000601902.5 linkuse as main transcript	c.151G>A	p.Val51Met	missense_variant	4/6	1		ENSP00000471379.1	M0R0Q6
ZNF470	ENST00000391709.4 linkuse as main transcript	c.151G>A	p.Val51Met	missense_variant	2/4	5		ENSP00000375590.3	Q6ECI4-1
ZNF470	ENST00000601059.1 linkuse as main transcript	n.609-154G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251344

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461600

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000603

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Nov 09, 2024

The c.151G>A (p.V51M) alteration is located in exon 4 (coding exon 2) of the ZNF470 gene. This alteration results from a G to A substitution at nucleotide position 151, causing the valine (V) at amino acid position 51 to be replaced by a methionine (M). 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

0.26

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

.;D;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.;M

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

N;.;N

REVEL

Benign

0.21

Sift

Benign

0.080

T;.;T

Sift4G

Uncertain

0.038

D;T;D

Polyphen

1.0

D;.;D

Vest4

0.57

MutPred

0.75

Loss of methylation at K50 (P = 0.0195);Loss of methylation at K50 (P = 0.0195);Loss of methylation at K50 (P = 0.0195);

MVP

0.47

MPC

0.10

ClinPred

0.79

GERP RS

2.2

Varity_R

0.17

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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