17-16553358-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_020653.4(ZNF287):c.784C>T(p.His262Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF287 NM_020653.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.101

Genes affected

ZNF287 (HGNC:13502): (zinc finger protein 287) This gene encodes a member of the krueppel family of zinc finger proteins, suggesting a role as a transcription factor. Its specific function has not been determined. This gene is located near the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZNF287
• BP4: Computational evidence support a benign effect (MetaRNN=0.053729683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF287	NM_020653.4	c.784C>T	p.His262Tyr	missense_variant	6/6	ENST00000395825.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF287	ENST00000395825.4	c.784C>T	p.His262Tyr	missense_variant	6/6	1	NM_020653.4	P1
ZNF287	ENST00000395824.5	c.784C>T	p.His262Tyr	missense_variant	6/6	1		P1
ZNF287	ENST00000498796.1	n.188C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459284 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725904

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 26, 2022

The c.784C>T (p.H262Y) alteration is located in exon 6 (coding exon 5) of the ZNF287 gene. This alteration results from a C to T substitution at nucleotide position 784, causing the histidine (H) at amino acid position 262 to be replaced by a tyrosine (Y). 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	0.067
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	4.3
Dann	Benign	0.81
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0012	N
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.16	N;N
REVEL	Benign	0.019
Sift	Benign	0.038	D;D
Sift4G	Benign	1.0	T;T
Vest4		0.079
MVP		0.043
MPC		0.47
ClinPred		0.093	T
GERP RS		1.2
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs1906826200; hg19: chr17-16456672;