Variant 20-53575750-G-A 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_006526.3(ZNF217):c.3014C>T(p.Pro1005Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,176 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF217
NM_006526.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

ZNF217 (HGNC:13009): (zinc finger protein 217) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in mitochondrion and nuclear speck. Part of histone deacetylase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF217 links:

(HGNC:):

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=0.09781492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF217	NM_006526.3 linkuse as main transcript	c.3014C>T	p.Pro1005Leu	missense_variant	4/6	ENST00000371471.7	NP_006517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF217	ENST00000371471.7 linkuse as main transcript	c.3014C>T	p.Pro1005Leu	missense_variant	4/6	5	NM_006526.3	ENSP00000360526	P1
ZNF217	ENST00000302342.3 linkuse as main transcript	c.3014C>T	p.Pro1005Leu	missense_variant	3/5	1		ENSP00000304308	P1
	ENST00000424252.2 linkuse as main transcript	n.2389G>A		non_coding_transcript_exon_variant	6/6	2
ZNF217	ENST00000437222.1 linkuse as main transcript	c.278C>T	p.Pro93Leu	missense_variant	1/2	2		ENSP00000394010

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000424

AC:

AN:

235668

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127262

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:

0.00000932

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715220

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:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Apr 26, 2023

The c.3014C>T (p.P1005L) alteration is located in exon 3 (coding exon 3) of the ZNF217 gene. This alteration results from a C to T substitution at nucleotide position 3014, causing the proline (P) at amino acid position 1005 to be replaced by a leucine (L). 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

0.075

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.9

DANN

Benign

0.96

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.60

.;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.098

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.089

Sift

Benign

0.26

T;T;D

Sift4G

Benign

0.33

T;T;D

Polyphen

0.0

B;B;.

Vest4

0.045

MutPred

0.18

Loss of glycosylation at P1005 (P = 0.016);Loss of glycosylation at P1005 (P = 0.016);.;

MVP

0.043

MPC

0.23

ClinPred

0.068

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.042

gMVP

0.016

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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