chr16-3115844-G-A

Variant names:

• chr16-3115844-G-A
• rs201059051
• NM_001042428.2:c.287G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001042428.2(ZNF205):​c.287G>A​(p.Arg96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,613,576 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/24 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. R96W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: ZNF205 NM_001042428.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 3 publications found

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]

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF205	NM_001042428.2	c.287G>A	p.Arg96Gln	missense_variant	Exon 4 of 7	ENST00000219091.9	NP_001035893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF205	ENST00000219091.9	c.287G>A	p.Arg96Gln	missense_variant	Exon 4 of 7	5	NM_001042428.2	ENSP00000219091.4

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152208 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000197 AC: 49 AN: 248506 AF XY: 0.000200

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00149

Gnomad NFE exome AF: 0.0000449

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000166 AC: 242 AN: 1461368 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 127 AN XY: 726980

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.000476 AC: 41 AN: 86222

European-Finnish (FIN) AF: 0.00122 AC: 65 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.000113 AC: 126 AN: 1111778

Other (OTH) AF: 0.000116 AC: 7 AN: 60356

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152208 Hom.: 1 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74352

African (AFR) AF: 0.0000724 AC: 3 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000390 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.66
DEOGEN2	Benign	0.012	T;T;T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.48	.;.;T;T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.0070	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;N;N;.;.
PhyloP100		-0.27
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.51	N;N;.;N;N
REVEL	Benign	0.018
Sift	Benign	0.72	T;T;.;T;T
Sift4G	Benign	0.96	T;T;T;T;T
Polyphen		0.0010	B;B;B;.;.
Vest4		0.14
MVP		0.25
MPC		0.11
ClinPred		0.0070	T
GERP RS		-2.1
PromoterAI		-0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.014
gMVP		0.062
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.74		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.74		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201059051; hg19: chr16-3165845;