17-15716134-C-T

Position:

• chr17-15716134-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130842.2(ZNF286A):​c.410C>T​(p.Ala137Val) 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. 15/21 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: 0.585

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05468455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF286A	NM_001130842.2	c.410C>T	p.Ala137Val	missense_variant	6/6	ENST00000583566.6	NP_001124314.1
ZNF286A-TBC1D26	NR_171000.1	n.718C>T		non_coding_transcript_exon_variant	6/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF286A	ENST00000583566.6	c.410C>T	p.Ala137Val	missense_variant	6/6	1	NM_001130842.2	ENSP00000464063	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.410C>T (p.A137V) alteration is located in exon 6 (coding exon 5) of the ZNF286A gene. This alteration results from a C to T substitution at nucleotide position 410, causing the alanine (A) at amino acid position 137 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.62
DEOGEN2	Benign	0.0028	T;.;T;.;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.18	T;T;.;T;.
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.055	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.37	N;.;N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.52	N;.;.;.;.
REVEL	Benign	0.040
Sift	Benign	0.44	T;.;.;.;.
Sift4G	Benign	0.67	T;T;T;D;T
Polyphen		0.0	B;.;B;.;B
Vest4		0.039
MutPred		0.23		Loss of ubiquitination at K135 (P = 0.0935);.;Loss of ubiquitination at K135 (P = 0.0935);.;Loss of ubiquitination at K135 (P = 0.0935);
MVP		0.085
MPC		1.2
ClinPred		0.049	T
GERP RS		2.2
Varity_R		0.048
gMVP		0.058

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-15619448;