19-37127862-C-T

Variant names:

• chr19-37127862-C-T
• NM_144689.5:c.871C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144689.5(ZNF420):​c.871C>T​(p.Leu291Phe) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF420 NM_144689.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.35
• Publications: 0 publications found

Genes affected

ZNF420 (HGNC:20649): (zinc finger protein 420) The protein encoded by this gene is a KRAB-type zinc finger protein that negatively-regulates p53-mediated apoptosis. Under stress conditions, the encoded protein is phosphorylated by ATM and dissociates from p53, which activates p53 and initiates apoptosis. [provided by RefSeq, Jul 2016]

ENSG00000267360 (HGNC:):

ZNF585A (HGNC:26305): (zinc finger protein 585A) Predicted to enable DNA-binding transcription activator 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096001714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144689.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF420	NM_144689.5	MANE Select	c.871C>T	p.Leu291Phe	missense	Exon 5 of 5	NP_653290.2
	ZNF420	NM_001329515.3		c.871C>T	p.Leu291Phe	missense	Exon 5 of 6	NP_001316444.1
	ZNF420	NM_001329516.3		c.871C>T	p.Leu291Phe	missense	Exon 4 of 5	NP_001316445.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF420	ENST00000337995.4	TSL:1 MANE Select	c.871C>T	p.Leu291Phe	missense	Exon 5 of 5	ENSP00000338770.2	Q8TAQ5-1
	ENSG00000267360	ENST00000588873.1	TSL:5	c.253+28003G>A		intron	N/A	ENSP00000465212.1	K7EJK4
	ZNF420	ENST00000876809.1		c.871C>T	p.Leu291Phe	missense	Exon 5 of 5	ENSP00000546868.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.56	N
PhyloP100		-1.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.12
Sift	Benign	0.70	T
Sift4G	Benign	0.70	T
Polyphen		0.063	B
Vest4		0.14
MutPred		0.58		Loss of helix (P = 0.1299)
MVP		0.26
MPC		0.65
ClinPred		0.074	T
GERP RS		2.9
PromoterAI		-0.0022	Neutral
Varity_R		0.042
gMVP		0.017
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr19-37618764;