Variant chr18-25062732-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_015461.3(ZNF521):c.3916A>G(p.Met1306Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000625 in 1,280,758 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

ZNF521
NM_015461.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.78

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, ZNF521

BP4

Computational evidence support a benign effect (MetaRNN=0.14387336).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF521	NM_015461.3 linkuse as main transcript	c.3916A>G	p.Met1306Val	missense_variant	8/8	ENST00000361524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF521	ENST00000361524.8 linkuse as main transcript	c.3916A>G	p.Met1306Val	missense_variant	8/8	1	NM_015461.3	P1
ZNF521	ENST00000584787.5 linkuse as main transcript	c.3256A>G	p.Met1086Val	missense_variant	7/7	1
ZNF521	ENST00000399425.6 linkuse as main transcript	c.*261A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	1
ZNF521	ENST00000538137.6 linkuse as main transcript	c.3916A>G	p.Met1306Val	missense_variant	8/8	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000162

AC:

AN:

123308

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000312

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000454

AC:

AN:

220200

Hom.:

AF XY:

0.00000834

AC XY:

AN XY:

119956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000964

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000518

AC:

AN:

1157450

Hom.:

Cov.:

AF XY:

0.00000343

AC XY:

AN XY:

583842

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:

0.0000234

Gnomad4 NFE exome

AF:

0.00000572

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000162

AC:

AN:

123308

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

57382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000312

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000285

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

-0.069

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.0060

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

N;.;N

MutationTaster

Benign

0.87

N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.0

N;.;.

REVEL

Benign

0.059

Sift

Uncertain

0.0080

D;.;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.029

B;.;B

Vest4

0.33

MutPred

0.34

Loss of disorder (P = 0.0642);.;Loss of disorder (P = 0.0642);

MVP

0.043

MPC

1.3

ClinPred

0.14

GERP RS

5.5

Varity_R

0.33

gMVP

0.18

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