17-16563752-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_020653.4(ZNF287):c.575A>G(p.Lys192Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 0.0000096 (0 hom.)
• Consequence: ZNF287 NM_020653.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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 Uncertain_significance. Variant got 2 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=0.3266783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF287	NM_020653.4	c.575A>G	p.Lys192Arg	missense_variant	4/6	ENST00000395825.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF287	ENST00000395825.4	c.575A>G	p.Lys192Arg	missense_variant	4/6	1	NM_020653.4	P1
ZNF287	ENST00000395824.5	c.575A>G	p.Lys192Arg	missense_variant	4/6	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461734 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727150

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: 0.0000126

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

Dec 03, 2021

The c.575A>G (p.K192R) alteration is located in exon 4 (coding exon 3) of the ZNF287 gene. This alteration results from a A to G substitution at nucleotide position 575, causing the lysine (K) at amino acid position 192 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Uncertain	23
Dann	Uncertain	0.99
Eigen	Benign	0.040
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.51	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.88	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.88	N;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.54
MVP		0.12
MPC		1.1
ClinPred		0.80	D
GERP RS		4.0
gMVP		0.39

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: rs1907583450; hg19: chr17-16467066;