17-15708212-A-C

Variant names:

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

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>C​(p.Lys100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,593,620 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF286A NM_001130842.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.052615047).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130842.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF286A	NM_001130842.2	MANE Select	c.299A>C	p.Lys100Thr	missense	Exon 5 of 6	NP_001124314.1	Q9HBT8-1
	ZNF286A	NM_001288642.2		c.428A>C	p.Lys143Thr	missense	Exon 5 of 6	NP_001275571.1
	ZNF286A	NM_020652.3		c.299A>C	p.Lys100Thr	missense	Exon 5 of 6	NP_065703.1	Q9HBT8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF286A	ENST00000583566.6	TSL:1 MANE Select	c.299A>C	p.Lys100Thr	missense	Exon 5 of 6	ENSP00000464063.1	Q9HBT8-1
	ZNF286A	ENST00000464847.6	TSL:1	c.299A>C	p.Lys100Thr	missense	Exon 4 of 5	ENSP00000464218.1	Q9HBT8-1
	ZNF286A	ENST00000395894.6	TSL:1	c.299A>C	p.Lys100Thr	missense	Exon 5 of 6	ENSP00000379231.2	J3KSW0

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000825 AC: 2 AN: 242366 AF XY: 0.00000759

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1441518 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 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: 0.00000272 AC: 3 AN: 1102174

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.013	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.91	N
PhyloP100		0.42
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.064
Sift	Benign	0.32	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.28		Gain of phosphorylation at K100 (P = 0.0127)
MVP		0.43
MPC		0.074
ClinPred		0.082	T
GERP RS		1.3
Varity_R		0.041
gMVP		0.14

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

Other links and lift over

dbSNP: rs1467218222; hg19: chr17-15611526;