Variant 9-106923483-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_StrongBP6_ModerateBS1BS2_Supporting

The NM_021224.6(ZNF462):c.100A>G(p.Thr34Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF462
NM_021224.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.83

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 Benign. Variant got -10 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZNF462. . Gene score misZ 3.3514 (greater than the threshold 3.09). Trascript score misZ 5.0931 (greater than threshold 3.09). GenCC has associacion of gene with weiss-kruszka syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.05351928).

BP6

Variant 9-106923483-A-G is Benign according to our data. Variant chr9-106923483-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3258165.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000178 (26/1461894) while in subpopulation AMR AF= 0.000447 (20/44724). AF 95% confidence interval is 0.000296. There are 0 homozygotes in gnomad4_exome. There are 10 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 26 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	UniProt
ZNF462	NM_021224.6 linkuse as main transcript	c.100A>G	p.Thr34Ala	missense_variant	2/13	ENST00000277225.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF462	ENST00000277225.10 linkuse as main transcript	c.100A>G	p.Thr34Ala	missense_variant	2/13	1	NM_021224.6	P1	Q96JM2-1
ZNF462	ENST00000472574.1 linkuse as main transcript	c.100A>G	p.Thr34Ala	missense_variant	2/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000835

AC:

AN:

251496

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000741

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.086

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.96

N;.

REVEL

Benign

0.14

Sift

Benign

0.43

T;.

Sift4G

Benign

0.44

T;D

Polyphen

0.12

B;.

Vest4

0.33

MutPred

0.20

Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);

MVP

0.068

MPC

0.32

ClinPred

0.069

GERP RS

5.9

Varity_R

0.20

gMVP

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over