Genetic Variant ZNF205:p.Ile49Val (chr16-3115442-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001042428.2(ZNF205):c.145A>G(p.Ile49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF205
NM_001042428.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.299

Publications

0 publications found

Variant links:

Genes affected

ZNF205 (HGNC:12996): (zinc finger protein 205) Predicted to enable DNA-binding transcription factor 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; positive regulation of hydrogen peroxide biosynthetic process; and positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF205 links:

ZNF213-AS1 (HGNC:50505): (ZNF213 antisense RNA 1 (head to head))

ZNF213-AS1 links:

ZNF205-AS1 (HGNC:28586): (ZNF205 antisense RNA 1)

ZNF205-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0450781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF205	NM_001042428.2 link	c.145A>G	p.Ile49Val	missense_variant	Exon 3 of 7	ENST00000219091.9	NP_001035893.1	O95201

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF205	ENST00000219091.9 link	c.145A>G	p.Ile49Val	missense_variant	Exon 3 of 7	5	NM_001042428.2	ENSP00000219091.4		O95201

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460258

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.00

AC:

AN:

86012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1111228

Other (OTH)

AF:

0.00

AC:

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.145A>G (p.I49V) alteration is located in exon 3 (coding exon 2) of the ZNF205 gene. This alteration results from a A to G substitution at nucleotide position 145, causing the isoleucine (I) at amino acid position 49 to be replaced by a valine (V). 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

0.079

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.6

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.025

T;T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0084

LIST_S2

Benign

0.61

.;.;T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.045

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L;.;.

PhyloP100

-0.30

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.19

N;N;.;N;N

REVEL

Benign

0.029

Sift

Benign

0.11

T;T;.;T;T

Sift4G

Benign

0.33

T;T;T;D;T

Polyphen

0.0010

B;B;B;.;.

Vest4

0.080

MutPred

0.097

Gain of methylation at K50 (P = 0.0474);Gain of methylation at K50 (P = 0.0474);Gain of methylation at K50 (P = 0.0474);Gain of methylation at K50 (P = 0.0474);Gain of methylation at K50 (P = 0.0474);

MVP

0.15

MPC

0.095

ClinPred

0.057

GERP RS

-1.7

PromoterAI

0.0056

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.061

Mutation Taster

=100/0

polymorphism

(source)

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

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chr16-3115442-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over