Variant 9-106924176-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The NM_021224.6(ZNF462):c.264C>A(p.His88Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,808 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF462
NM_021224.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

ZNF462 (HGNC:21684): (zinc finger protein 462) The protein encoded by this gene belongs to C2H2-type zinc finger family of proteins. It contains multiple C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ZNF462 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05507064).

BS2

High AC in GnomAdExome4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF462	NM_021224.6 link	c.264C>A	p.His88Gln	missense_variant	3/13	ENST00000277225.10	NP_067047.4	Q96JM2-1Q63HJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF462	ENST00000277225.10 link	c.264C>A	p.His88Gln	missense_variant	3/13	1	NM_021224.6	ENSP00000277225.5		Q96JM2-1
ZNF462	ENST00000472574.1 link	c.264C>A	p.His88Gln	missense_variant	3/4	4		ENSP00000476222.1		U3KQU3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249104

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000205

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:

0.00000480

AC:

AN:

1459808

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

725976

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000158

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.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2024

The c.264C>A (p.H88Q) alteration is located in exon 3 (coding exon 2) of the ZNF462 gene. This alteration results from a C to A substitution at nucleotide position 264, causing the histidine (H) at amino acid position 88 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

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.55

N;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.053

Sift

Benign

0.20

T;.

Sift4G

Benign

0.48

T;T

Polyphen

0.0020

B;.

Vest4

0.14

MutPred

0.14

Gain of glycosylation at P90 (P = 0.0915);Gain of glycosylation at P90 (P = 0.0915);

MVP

0.068

MPC

0.34

ClinPred

0.049

GERP RS

4.0

Varity_R

0.057

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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