Variant 19-56576843-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001001668.4(ZNF470):c.414C>A(p.Asn138Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000348 in 1,438,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 0.0000035 ( 0 hom. )

Consequence

ZNF470
NM_001001668.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0170

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:

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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=0.055973083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF470	NM_001001668.4 linkuse as main transcript	c.414C>A	p.Asn138Lys	missense_variant	6/6	ENST00000330619.13	NP_001001668.3	Q6ECI4-1
ZNF470	XM_047438804.1 linkuse as main transcript	c.414C>A	p.Asn138Lys	missense_variant	7/7		XP_047294760.1
ZNF470	XM_047438805.1 linkuse as main transcript	c.261C>A	p.Asn87Lys	missense_variant	5/5		XP_047294761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF470	ENST00000330619.13 linkuse as main transcript	c.414C>A	p.Asn138Lys	missense_variant	6/6	1	NM_001001668.4	ENSP00000333223.7		Q6ECI4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000216

AC:

AN:

231242

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

125640

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 SAS exome

AF:

0.000184

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000348

AC:

AN:

1438816

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

715582

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:

0.0000610

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

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

Sep 30, 2024

The c.414C>A (p.N138K) alteration is located in exon 6 (coding exon 4) of the ZNF470 gene. This alteration results from a C to A substitution at nucleotide position 414, causing the asparagine (N) at amino acid position 138 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.3

DANN

Benign

0.85

DEOGEN2

Benign

0.0035

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.010

.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.035

Sift

Benign

0.83

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.36

B;B

Vest4

0.11

MutPred

0.32

Gain of ubiquitination at N138 (P = 0.0219);Gain of ubiquitination at N138 (P = 0.0219);

MVP

0.36

MPC

0.015

ClinPred

0.065

GERP RS

1.9

Varity_R

0.056

gMVP

0.032

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