chr17-15708212-A-G

Variant names:

• chr17-15708212-A-G
• rs1467218222
• NM_001130842.2:c.299A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130842.2(ZNF286A):​c.299A>G​(p.Lys100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,441,518 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. K100T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ZNF286A NM_001130842.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 0 publications found

Genes affected

ZNF286A (HGNC:13501): (zinc finger protein 286A) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF286A-TBC1D26 (HGNC:55384): (ZNF286A-TBC1D26 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ZNF286A and TBC1D26 genes. This transcript is thought to be non-coding because it would be subject to nonsense-mediated mRNA decay (NMD). [provided by RefSeq, Nov 2020]

ACMG classification

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=0.04533416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF286A	NM_001130842.2	c.299A>G	p.Lys100Arg	missense_variant	Exon 5 of 6	ENST00000583566.6	NP_001124314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF286A	ENST00000583566.6	c.299A>G	p.Lys100Arg	missense_variant	Exon 5 of 6	1	NM_001130842.2	ENSP00000464063.1
ZNF286A-TBC1D26	ENST00000413242.6	n.299A>G		non_coding_transcript_exon_variant	Exon 5 of 17	2		ENSP00000458062.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1441518 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 717534

African (AFR) AF: 0.00 AC: 0 AN: 32672

American (AMR) AF: 0.00 AC: 0 AN: 42092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25494

East Asian (EAS) AF: 0.00 AC: 0 AN: 38422

South Asian (SAS) AF: 0.00 AC: 0 AN: 83246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00000454 AC: 5 AN: 1102174

Other (OTH) AF: 0.00 AC: 0 AN: 59146

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0010	T;.;T;T;.;.;.;T;T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.010	T;T;.;T;.;T;T;.;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.045	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.89	N;.;N;.;.;.;.;N;.;.
PhyloP100		0.42
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.21	N;.;.;.;N;.;.;.;N;.
REVEL	Benign	0.054
Sift	Benign	0.071	T;.;.;.;T;.;.;.;T;.
Sift4G	Benign	0.32	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.;.;B;.;.
Vest4		0.059
MutPred		0.22		Loss of ubiquitination at K100 (P = 0.0244);.;Loss of ubiquitination at K100 (P = 0.0244);.;Loss of ubiquitination at K100 (P = 0.0244);.;Loss of ubiquitination at K100 (P = 0.0244);Loss of ubiquitination at K100 (P = 0.0244);Loss of ubiquitination at K100 (P = 0.0244);.;
MVP		0.29
MPC		0.054
ClinPred		0.096	T
GERP RS		1.3
Varity_R		0.022
gMVP		0.083
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1467218222; hg19: chr17-15611526;