20-53576345-C-T

Position:

• chr20-53576345-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006526.3(ZNF217):​c.2419G>A​(p.Gly807Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF217 NM_006526.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

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]

ACMG classification

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=0.20988235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF217	NM_006526.3	c.2419G>A	p.Gly807Arg	missense_variant	4/6	ENST00000371471.7	NP_006517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF217	ENST00000371471.7	c.2419G>A	p.Gly807Arg	missense_variant	4/6	5	NM_006526.3	ENSP00000360526.2
ZNF217	ENST00000302342.3	c.2419G>A	p.Gly807Arg	missense_variant	3/5	1		ENSP00000304308.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.2419G>A (p.G807R) alteration is located in exon 3 (coding exon 3) of the ZNF217 gene. This alteration results from a G to A substitution at nucleotide position 2419, causing the glycine (G) at amino acid position 807 to be replaced by an arginine (R). 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	0.32
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.0033
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.098
Sift	Benign	0.040	D;D
Sift4G	Uncertain	0.048	D;D
Polyphen		1.0	D;D
Vest4		0.37
MutPred		0.19		Gain of MoRF binding (P = 0.0349);Gain of MoRF binding (P = 0.0349);
MVP		0.13
MPC		0.90
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.11
gMVP		0.077

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

Other links and lift over

dbSNP: rs1988267974; hg19: chr20-52192884;