Variant 20-53575980-G-T 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_006526.3(ZNF217):c.2784C>A(p.Asp928Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

ZNF217
NM_006526.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.94

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:

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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=0.066122115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF217	NM_006526.3 linkuse as main transcript	c.2784C>A	p.Asp928Glu	missense_variant	4/6	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.2784C>A	p.Asp928Glu	missense_variant	4/6	5	NM_006526.3	ENSP00000360526.2	O75362
ZNF217	ENST00000302342.3 linkuse as main transcript	c.2784C>A	p.Asp928Glu	missense_variant	3/5	1		ENSP00000304308.3	O75362
ZNF217	ENST00000437222.1 linkuse as main transcript	c.48C>A	p.Asp16Glu	missense_variant	1/2	2		ENSP00000394010.1	Q9BZ31

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251402

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Jul 19, 2023

The c.2784C>A (p.D928E) alteration is located in exon 3 (coding exon 3) of the ZNF217 gene. This alteration results from a C to A substitution at nucleotide position 2784, causing the aspartic acid (D) at amino acid position 928 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

Benign

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0010

DANN

Benign

0.89

DEOGEN2

Benign

0.054

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.40

.;T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

L;L;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.81

N;N;N

REVEL

Benign

0.0020

Sift

Benign

0.51

T;T;T

Sift4G

Benign

0.71

T;T;D

Polyphen

0.015

B;B;.

Vest4

0.032

MutPred

0.38

Loss of phosphorylation at S923 (P = 0.2272);Loss of phosphorylation at S923 (P = 0.2272);.;

MVP

0.043

MPC

0.22

ClinPred

0.040

GERP RS

-7.6

Varity_R

0.023

gMVP

0.050

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