Variant 3-44734983-A-G 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_001258280.2(ZNF501):c.562A>G(p.Lys188Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,614,058 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF501
NM_001258280.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

Variant links:

Genes affected

ZNF501 (HGNC:23717): (zinc finger protein 501) Enables sequence-specific double-stranded DNA binding activity. Involved in Golgi organization. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF501 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=0.19203809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF501	NM_001258280.2 linkuse as main transcript	c.562A>G	p.Lys188Glu	missense_variant	3/3	ENST00000620116.5	NP_001245209.1
ZNF501	NM_145044.4 linkuse as main transcript	c.562A>G	p.Lys188Glu	missense_variant	3/3		NP_659481.2
ZNF501	XM_047447399.1 linkuse as main transcript	c.562A>G	p.Lys188Glu	missense_variant	3/3		XP_047303355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF501	ENST00000620116.5 linkuse as main transcript	c.562A>G	p.Lys188Glu	missense_variant	3/3	4	NM_001258280.2	ENSP00000482632	P1	Q96CX3-1
ZNF501	ENST00000396048.6 linkuse as main transcript	c.562A>G	p.Lys188Glu	missense_variant	3/3	1		ENSP00000379363	P1	Q96CX3-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

250320

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

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:

0.0000144

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000470

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

AF:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.0000412

AC:

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

Aug 02, 2021

The c.562A>G (p.K188E) alteration is located in exon 3 (coding exon 1) of the ZNF501 gene. This alteration results from a A to G substitution at nucleotide position 562, causing the lysine (K) at amino acid position 188 to be replaced by a glutamic acid (E). 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.57

M_CAP

Benign

0.0067

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.91

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.7

D;.

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.27

MutPred

0.39

Loss of methylation at K188 (P = 0.0013);Loss of methylation at K188 (P = 0.0013);

MVP

0.38

MPC

0.033

ClinPred

0.56

GERP RS

3.1

Varity_R

0.51

gMVP

0.0073

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