17-15716062-T-C

Variant names:

• chr17-15716062-T-C
• rs1197492300
• NM_001130842.2:c.338T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001288644.2(ZNF286A):​c.2T>C​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZNF286A NM_001288644.2 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00400
• Publications: 1 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: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 64 codons. Genomic position: 15716250. Lost 0.154 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288644.2. 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.338T>C	p.Met113Thr	missense	Exon 6 of 6	NP_001124314.1	Q9HBT8-1
	ZNF286A	NM_001288644.2		c.2T>C	p.Met1?	start_lost	Exon 4 of 4	NP_001275573.2	A1A525
	ZNF286A	NM_001288645.2		c.2T>C	p.Met1?	start_lost	Exon 6 of 6	NP_001275574.1	A1A525

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF286A	ENST00000583566.6	TSL:1 MANE Select	c.338T>C	p.Met113Thr	missense	Exon 6 of 6	ENSP00000464063.1	Q9HBT8-1
	ZNF286A	ENST00000464847.6	TSL:1	c.338T>C	p.Met113Thr	missense	Exon 5 of 5	ENSP00000464218.1	Q9HBT8-1
	ZNF286A	ENST00000395894.6	TSL:1	c.*46T>C		3_prime_UTR	Exon 6 of 6	ENSP00000379231.2	J3KSW0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461530 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727072

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000624 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	0.065
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.35
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.097	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.0040
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.083
Sift	Benign	0.15	T
Sift4G	Benign	0.37	T
Polyphen		0.0010	B
Vest4		0.052
MutPred		0.23		Gain of phosphorylation at M113 (P = 0.0168)
MVP		0.27
MPC		0.073
ClinPred		0.095	T
GERP RS		0.38
Varity_R		0.060
gMVP		0.12
Mutation Taster		=97/3	polymorphism

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: rs1197492300; hg19: chr17-15619376;