Variant chr20-53571809-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006526.3(ZNF217):c.3082C>A(p.Gln1028Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,338 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF217
NM_006526.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF217	NM_006526.3 linkuse as main transcript	c.3082C>A	p.Gln1028Lys	missense_variant	5/6	ENST00000371471.7	NP_006517.1
LOC101927770	NR_110051.1 linkuse as main transcript	n.788-839G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF217	ENST00000371471.7 linkuse as main transcript	c.3082C>A	p.Gln1028Lys	missense_variant	5/6	5	NM_006526.3	ENSP00000360526	P1
ZNF217	ENST00000302342.3 linkuse as main transcript	c.3082C>A	p.Gln1028Lys	missense_variant	4/5	1		ENSP00000304308	P1
	ENST00000424252.2 linkuse as main transcript	n.788-839G>T		intron_variant, non_coding_transcript_variant		2
ZNF217	ENST00000437222.1 linkuse as main transcript	c.302-2545C>A		intron_variant		2		ENSP00000394010

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460338

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726450

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

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

Feb 12, 2024

The c.3082C>A (p.Q1028K) alteration is located in exon 4 (coding exon 4) of the ZNF217 gene. This alteration results from a C to A substitution at nucleotide position 3082, causing the glutamine (Q) at amino acid position 1028 to be replaced by a lysine (K). 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

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.75

MutPred

0.26

Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);

MVP

0.31

MPC

0.95

ClinPred

0.97

GERP RS

5.8

Varity_R

0.60

gMVP

0.27

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

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