17-15708206-C-T

Variant names:

• chr17-15708206-C-T
• rs144677558
• NM_001130842.2:c.293C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001130842.2(ZNF286A):​c.293C>T​(p.Pro98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00065 in 1,594,770 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (2 hom.)
• Consequence: ZNF286A NM_001130842.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0580
• Publications: 3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028776348).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF286A	NM_001130842.2	c.293C>T	p.Pro98Leu	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.293C>T	p.Pro98Leu	missense_variant	Exon 5 of 6	1	NM_001130842.2	ENSP00000464063.1
ZNF286A-TBC1D26	ENST00000413242.6	n.293C>T		non_coding_transcript_exon_variant	Exon 5 of 17	2		ENSP00000458062.1

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 151896 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000280 AC: 68 AN: 242948 AF XY: 0.000295

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.000537

Gnomad OTH exome AF: 0.000510

GnomAD4 exome AF: 0.000679 AC: 980 AN: 1442874 Hom.: 2 Cov.: 32 AF XY: 0.000663 AC XY: 476 AN XY: 718178

African (AFR) AF: 0.0000918 AC: 3 AN: 32662

American (AMR) AF: 0.0000473 AC: 2 AN: 42244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25506

East Asian (EAS) AF: 0.00 AC: 0 AN: 38476

South Asian (SAS) AF: 0.00 AC: 0 AN: 83458

European-Finnish (FIN) AF: 0.0000759 AC: 4 AN: 52688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.000830 AC: 915 AN: 1102928

Other (OTH) AF: 0.000945 AC: 56 AN: 59234

GnomAD4 genome AF: 0.000375 AC: 57 AN: 151896 Hom.: 0 Cov.: 32 AF XY: 0.000364 AC XY: 27 AN XY: 74174

African (AFR) AF: 0.000145 AC: 6 AN: 41336

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

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

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.000678 Hom.: 0

Bravo AF: 0.000533

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000280 AC: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.293C>T (p.P98L) alteration is located in exon 5 (coding exon 4) of the ZNF286A gene. This alteration results from a C to T substitution at nucleotide position 293, causing the proline (P) at amino acid position 98 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0068	.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.029	T;T
PhyloP100		-0.058
Vest4		0.18
MVP		0.41
ClinPred		0.042	T
GERP RS		0.47
Varity_R		0.028
Mutation Taster		=90/10	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: rs144677558; hg19: chr17-15611520;