Variant 19-56574500-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001001668.4(ZNF470):c.167A>G(p.Tyr56Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ZNF470
NM_001001668.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF470	NM_001001668.4 linkuse as main transcript	c.167A>G	p.Tyr56Cys	missense_variant	4/6	ENST00000330619.13	NP_001001668.3
ZNF470	XM_047438804.1 linkuse as main transcript	c.167A>G	p.Tyr56Cys	missense_variant	5/7		XP_047294760.1
ZNF470	XM_047438805.1 linkuse as main transcript	c.14A>G	p.Tyr5Cys	missense_variant	3/5		XP_047294761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF470	ENST00000330619.13 linkuse as main transcript	c.167A>G	p.Tyr56Cys	missense_variant	4/6	1	NM_001001668.4	ENSP00000333223	P1	Q6ECI4-1
ZNF470	ENST00000601902.5 linkuse as main transcript	c.167A>G	p.Tyr56Cys	missense_variant	4/6	1		ENSP00000471379
ZNF470	ENST00000391709.4 linkuse as main transcript	c.167A>G	p.Tyr56Cys	missense_variant	2/4	5		ENSP00000375590	P1	Q6ECI4-1
ZNF470	ENST00000601059.1 linkuse as main transcript	n.609-138A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251292

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135822

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

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 20, 2023

The c.167A>G (p.Y56C) alteration is located in exon 4 (coding exon 2) of the ZNF470 gene. This alteration results from a A to G substitution at nucleotide position 167, causing the tyrosine (Y) at amino acid position 56 to be replaced by a cysteine (C). 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

Uncertain

0.43

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.13

.;T;T

M_CAP

Benign

0.0053

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.;M

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-7.0

D;.;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;.;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.61

MVP

0.52

MPC

0.10

ClinPred

0.98

GERP RS

2.1

Varity_R

0.69

gMVP

0.22

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