Variant 20-53571842-C-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_006526.3(ZNF217):c.3049G>C(p.Val1017Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,616 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: not found (cov: 30)

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: 1.43

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:

ENSG00000197670 (HGNC:):

ENSG00000197670 links:

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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=0.12255487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF217	NM_006526.3 linkuse as main transcript	c.3049G>C	p.Val1017Leu	missense_variant	5/6	ENST00000371471.7	NP_006517.1	O75362

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF217	ENST00000371471.7 linkuse as main transcript	c.3049G>C	p.Val1017Leu	missense_variant	5/6	5	NM_006526.3	ENSP00000360526.2	O75362
ZNF217	ENST00000302342.3 linkuse as main transcript	c.3049G>C	p.Val1017Leu	missense_variant	4/5	1		ENSP00000304308.3	O75362
ZNF217	ENST00000437222.1 linkuse as main transcript	c.302-2578G>C		intron_variant		2		ENSP00000394010.1	Q9BZ31
ENSG00000197670	ENST00000424252.2 linkuse as main transcript	n.788-806C>G		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449616

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720928

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:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 12, 2023

The c.3049G>C (p.V1017L) alteration is located in exon 4 (coding exon 4) of the ZNF217 gene. This alteration results from a G to C substitution at nucleotide position 3049, causing the valine (V) at amino acid position 1017 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

0.21

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

0.071

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.058

Sift

Benign

0.28

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.22

B;B

Vest4

0.46

MutPred

0.18

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.15

MPC

0.41

ClinPred

0.77

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.078

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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