rs143337806

Variant names:

• chr19-37127812-C-G
• rs143337806
• NM_144689.5:c.821C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-37127812-C-G
• chr19-37127812-C-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.821C>G​(p.Thr274Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T274I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF420 NM_144689.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• 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=0.18998832).

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.821C>G	p.Thr274Ser	missense	Exon 5 of 5	NP_653290.2
	ZNF420	NM_001329515.3		c.821C>G	p.Thr274Ser	missense	Exon 5 of 6	NP_001316444.1
	ZNF420	NM_001329516.3		c.821C>G	p.Thr274Ser	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.821C>G	p.Thr274Ser	missense	Exon 5 of 5	ENSP00000338770.2	Q8TAQ5-1
	ENSG00000267360	ENST00000588873.1	TSL:5	c.253+28053G>C		intron	N/A	ENSP00000465212.1	K7EJK4
	ZNF420	ENST00000876809.1		c.821C>G	p.Thr274Ser	missense	Exon 5 of 5	ENSP00000546868.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461748 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.57	N
PhyloP100		0.21
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.068
Sift	Benign	0.11	T
Sift4G	Uncertain	0.057	T
Polyphen		0.94	P
Vest4		0.27
MutPred		0.37		Loss of catalytic residue at T274 (P = 0.0509)
MVP		0.26
MPC		0.43
ClinPred		0.32	T
GERP RS		2.9
PromoterAI		-0.015	Neutral
Varity_R		0.085
gMVP		0.011
Mutation Taster		=99/1	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

dbSNP: rs143337806; hg19: chr19-37618714;