chr17-16563185-A-C

Position:

• chr17-16563185-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000395825.4(ZNF287):​c.676T>G​(p.Trp226Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF287 ENST00000395825.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF287	NM_020653.4	c.676T>G	p.Trp226Gly	missense_variant	5/6	ENST00000395825.4	NP_065704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF287	ENST00000395825.4	c.676T>G	p.Trp226Gly	missense_variant	5/6	1	NM_020653.4	ENSP00000379169	P1
ZNF287	ENST00000395824.5	c.676T>G	p.Trp226Gly	missense_variant	5/6	1		ENSP00000379168	P1
ZNF287	ENST00000498796.1	n.80T>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251164 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461538 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 727102

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Apr 27, 2023

The c.676T>G (p.W226G) alteration is located in exon 5 (coding exon 4) of the ZNF287 gene. This alteration results from a T to G substitution at nucleotide position 676, causing the tryptophan (W) at amino acid position 226 to be replaced by a glycine (G). 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	Pathogenic	0.91
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.98
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.89	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Benign	0.15
Sift	Benign	0.088	T;T
Sift4G	Uncertain	0.0040	D;D
Vest4		0.53
MVP		0.043
MPC		1.7
ClinPred		0.99	D
GERP RS		4.4
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs748766060; hg19: chr17-16466499;