chr19-44386818-C-A

Position:

• chr19-44386818-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152354.6(ZNF285):​c.1427G>T​(p.Arg476Ile) 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. 10/17 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: ZNF285 NM_152354.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.749

Genes affected

ZNF285 (HGNC:13079): (zinc finger protein 285) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23710027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF285	NM_152354.6	c.1427G>T	p.Arg476Ile	missense_variant	4/4	ENST00000614994.5	NP_689567.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF285	ENST00000614994.5	c.1427G>T	p.Arg476Ile	missense_variant	4/4	1	NM_152354.6	ENSP00000483662	P2
ZNF285	ENST00000591679.5	c.1448G>T	p.Arg483Ile	missense_variant	5/5	4		ENSP00000464788	A2
ZNF285	ENST00000544719.6	c.1427G>T	p.Arg476Ile	missense_variant	4/4	5		ENSP00000439431	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

May 14, 2024

The c.1427G>T (p.R476I) alteration is located in exon 4 (coding exon 3) of the ZNF285 gene. This alteration results from a G to T substitution at nucleotide position 1427, causing the arginine (R) at amino acid position 476 to be replaced by an isoleucine (I). 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Benign	0.021
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.37	.;.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	D;D;D;D
REVEL	Benign	0.14
Sift4G	Uncertain	0.031	D;D;D
Vest4		0.21
MutPred		0.63		Loss of disorder (P = 0.0332);Loss of disorder (P = 0.0332);.;
MVP		0.32
ClinPred		0.87	D
GERP RS		3.5
gMVP		0.034

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: rs1971085052; hg19: chr19-44890980;