chr19-44387169-A-G

Position:

• chr19-44387169-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152354.6(ZNF285):​c.1076T>C​(p.Leu359Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF285 NM_152354.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF285	NM_152354.6	c.1076T>C	p.Leu359Pro	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.1076T>C	p.Leu359Pro	missense_variant	4/4	1	NM_152354.6	ENSP00000483662	P2
ZNF285	ENST00000591679.5	c.1097T>C	p.Leu366Pro	missense_variant	5/5	4		ENSP00000464788	A2
ZNF285	ENST00000544719.6	c.1076T>C	p.Leu359Pro	missense_variant	4/4	5		ENSP00000439431	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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 18, 2023

The c.1076T>C (p.L359P) alteration is located in exon 4 (coding exon 3) of the ZNF285 gene. This alteration results from a T to C substitution at nucleotide position 1076, causing the leucine (L) at amino acid position 359 to be replaced by a proline (P). 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	0.94
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	-0.073
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.015	.;.;T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.37	T
MutationTaster	Benign	1.0	D;N;N;N
REVEL	Benign	0.22
Sift4G	Benign	0.061	T;T;T
Vest4		0.58
MutPred		0.74		Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);.;
MVP		0.43
ClinPred		0.57	D
GERP RS		3.5
gMVP		0.21

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: chr19-44891331;