Variant chr18-25224520-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_StrongBP6_Moderate

The NM_015461.3(ZNF521):c.3398T>C(p.Val1133Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF521
NM_015461.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.07

Variant links:

Genes affected

ZNF521 (HGNC:24605): (zinc finger protein 521) Enables protein domain specific binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within neuron fate commitment. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF521 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, ZNF521

BP4

Computational evidence support a benign effect (MetaRNN=0.044669002).

BP6

Variant 18-25224520-A-G is Benign according to our data. Variant chr18-25224520-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2476494.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF521	NM_015461.3 linkuse as main transcript	c.3398T>C	p.Val1133Ala	missense_variant	4/8	ENST00000361524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF521	ENST00000361524.8 linkuse as main transcript	c.3398T>C	p.Val1133Ala	missense_variant	4/8	1	NM_015461.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727228

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.6

DANN

Benign

0.39

DEOGEN2

Benign

0.066

T;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.38

M_CAP

Benign

0.0052

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.2

N;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.63

N;.;.

REVEL

Benign

0.080

Sift

Benign

1.0

T;.;.

Sift4G

Benign

0.90

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.030

MutPred

0.35

Loss of methylation at K1132 (P = 0.0377);.;Loss of methylation at K1132 (P = 0.0377);

MVP

0.043

MPC

0.40

ClinPred

0.035

GERP RS

4.1

Varity_R

0.032

gMVP

0.16

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over