Variant 5-122152000-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_207317.3(ZNF474):c.10G>A(p.Gly4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,434 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: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF474
NM_207317.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.572

Variant links:

Genes affected

ZNF474 (HGNC:23245): (zinc finger protein 474) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF474 links:

(HGNC:):

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=0.08064574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF474	NM_207317.3 linkuse as main transcript	c.10G>A	p.Gly4Arg	missense_variant	2/2	ENST00000296600.5	NP_997200.1
ZNF474-AS1	XR_007058915.1 linkuse as main transcript	n.272-1397C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF474	ENST00000296600.5 linkuse as main transcript	c.10G>A	p.Gly4Arg	missense_variant	2/2	1	NM_207317.3	ENSP00000296600
	ENST00000504829.1 linkuse as main transcript	n.233+2624C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245662

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

132992

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456434

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724502

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 10, 2021

The c.10G>A (p.G4R) alteration is located in exon 2 (coding exon 1) of the ZNF474 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the glycine (G) at amino acid position 4 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.0035

T;.;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.081

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.50

N;D;D

REVEL

Benign

0.031

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.035

D;D;D

Polyphen

0.45

B;.;.

Vest4

0.072

MutPred

0.23

Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);

MVP

0.19

MPC

0.011

ClinPred

0.18

GERP RS

3.1

Varity_R

0.095

gMVP

0.017

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