chr20-53576225-C-A

Position:

• chr20-53576225-C-A

Variant summary

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

The NM_006526.3(ZNF217):​c.2539G>T​(p.Val847Phe) 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. 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: 33)
• Consequence: ZNF217 NM_006526.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.283

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=0.09582117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF217	NM_006526.3	c.2539G>T	p.Val847Phe	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.2539G>T	p.Val847Phe	missense_variant	4/6	5	NM_006526.3	ENSP00000360526	P1
ZNF217	ENST00000302342.3	c.2539G>T	p.Val847Phe	missense_variant	3/5	1		ENSP00000304308	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Apr 22, 2024

The c.2539G>T (p.V847F) alteration is located in exon 3 (coding exon 3) of the ZNF217 gene. This alteration results from a G to T substitution at nucleotide position 2539, causing the valine (V) at amino acid position 847 to be replaced by a phenylalanine (F). 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	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.65	.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.068
Sift	Benign	0.62	T;T
Sift4G	Uncertain	0.036	D;D
Polyphen		0.98	D;D
Vest4		0.16
MutPred		0.083		Loss of glycosylation at S846 (P = 0.1534);Loss of glycosylation at S846 (P = 0.1534);
MVP		0.068
MPC		0.41
ClinPred		0.19	T
GERP RS		1.1
Varity_R		0.039
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-52192764;