Variant 3-44735092-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001258280.2(ZNF501):c.671A>G(p.Glu224Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,198 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: 𝑓 0.0000066 ( 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: 0.509

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01985386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF501	NM_001258280.2 linkuse as main transcript	c.671A>G	p.Glu224Gly	missense_variant	3/3	ENST00000620116.5	NP_001245209.1
ZNF501	NM_145044.4 linkuse as main transcript	c.671A>G	p.Glu224Gly	missense_variant	3/3		NP_659481.2
ZNF501	XM_047447399.1 linkuse as main transcript	c.671A>G	p.Glu224Gly	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.671A>G	p.Glu224Gly	missense_variant	3/3	4	NM_001258280.2	ENSP00000482632	P1	Q96CX3-1
ZNF501	ENST00000396048.6 linkuse as main transcript	c.671A>G	p.Glu224Gly	missense_variant	3/3	1		ENSP00000379363	P1	Q96CX3-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250026

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135612

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727222

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:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74500

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:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jul 09, 2021

The c.671A>G (p.E224G) 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 671, causing the glutamic acid (E) at amino acid position 224 to be replaced by a glycine (G). 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

0.055

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.010

M_CAP

Benign

0.0031

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.7

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

2.8

N;.

REVEL

Benign

0.097

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.21

MVP

0.055

MPC

0.036

ClinPred

0.19

GERP RS

-0.99

Varity_R

0.059

gMVP

0.018

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