Variant 19-57291356-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_006635.4(ZNF460):c.815G>A(p.Arg272Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ZNF460
NM_006635.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.734

Variant links:

Genes affected

ZNF460 (HGNC:21628): (zinc finger protein 460) Zinc finger proteins, such as ZNF272, interact with nucleic acids and have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See ZFP93 (MIM 604749) for additional information on zinc finger proteins.[supplied by OMIM, May 2004]

ZNF460 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=0.14369035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF460	NM_006635.4 linkuse as main transcript	c.815G>A	p.Arg272Gln	missense_variant	3/3	ENST00000360338.4	NP_006626.3
ZNF460	NM_001330622.2 linkuse as main transcript	c.692G>A	p.Arg231Gln	missense_variant	3/3		NP_001317551.1
ZNF460	XM_047438079.1 linkuse as main transcript	c.794G>A	p.Arg265Gln	missense_variant	3/3		XP_047294035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF460	ENST00000360338.4 linkuse as main transcript	c.815G>A	p.Arg272Gln	missense_variant	3/3	1	NM_006635.4	ENSP00000353491	P1	Q14592-1
ZNF460	ENST00000537645.5 linkuse as main transcript	c.692G>A	p.Arg231Gln	missense_variant	3/3	2		ENSP00000446167		Q14592-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727240

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

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

Apr 22, 2024

The c.815G>A (p.R272Q) alteration is located in exon 3 (coding exon 3) of the ZNF460 gene. This alteration results from a G to A substitution at nucleotide position 815, causing the arginine (R) at amino acid position 272 to be replaced by a glutamine (Q). 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

0.54

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.067

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

.;D

Vest4

0.10

MutPred

0.59

.;Loss of catalytic residue at R272 (P = 0.0138);

MVP

0.14

MPC

1.7

ClinPred

0.85

GERP RS

0.70

Varity_R

0.13

gMVP

0.059

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