Genetic Variant NM_001042428.2:c.518A>C (chr16-3118938-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042428.2(ZNF205):c.518A>C(p.Gln173Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q173E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF205
NM_001042428.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.365

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20674694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF205	NM_001042428.2 link	c.518A>C	p.Gln173Pro	missense_variant	Exon 6 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.518A>C	p.Gln173Pro	missense_variant	Exon 6 of 7	5	NM_001042428.2	ENSP00000219091.4		O95201

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726986

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111952

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.21

T;T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.57

.;.;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L;.

PhyloP100

0.36

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.4

N;N;.;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;T;.;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.88

P;P;P;.

Vest4

0.41

MutPred

0.45

Gain of glycosylation at Q173 (P = 0.0381);Gain of glycosylation at Q173 (P = 0.0381);Gain of glycosylation at Q173 (P = 0.0381);Gain of glycosylation at Q173 (P = 0.0381);

MVP

0.66

MPC

0.12

ClinPred

0.43

GERP RS

4.6

Varity_R

0.34

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over