NM_001130842.2:c.500G>C

Variant names:

• chr17-15716224-G-C
• NM_001130842.2:c.500G>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.500G>C​(p.Gly167Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF286A NM_001130842.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.313
• 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=0.061621845).

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.500G>C	p.Gly167Ala	missense	Exon 6 of 6	NP_001124314.1	Q9HBT8-1
	ZNF286A	NM_001288642.2		c.629G>C	p.Gly210Ala	missense	Exon 6 of 6	NP_001275571.1
	ZNF286A	NM_020652.3		c.500G>C	p.Gly167Ala	missense	Exon 6 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.500G>C	p.Gly167Ala	missense	Exon 6 of 6	ENSP00000464063.1	Q9HBT8-1
	ZNF286A	ENST00000464847.6	TSL:1	c.500G>C	p.Gly167Ala	missense	Exon 5 of 5	ENSP00000464218.1	Q9HBT8-1
	ZNF286A	ENST00000395894.6	TSL:1	c.*208G>C		3_prime_UTR	Exon 6 of 6	ENSP00000379231.2	J3KSW0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.64
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.038	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.31
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.066
Sift	Benign	0.42	T
Sift4G	Benign	0.64	T
Polyphen		0.043	B
Vest4		0.15
MutPred		0.32		Gain of disorder (P = 0.1805)
MVP		0.18
MPC		1.3
ClinPred		0.062	T
GERP RS		2.3
Varity_R		0.044
gMVP		0.075

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

hg19: chr17-15619538;