rs747659700

Variant names:

• chr19-37091082-G-C
• rs747659700
• NM_144689.5:c.97G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144689.5(ZNF420):​c.97G>C​(p.Asp33His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,606,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF420 NM_144689.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3865674).

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.97G>C	p.Asp33His	missense	Exon 4 of 5	NP_653290.2
	ZNF420	NM_001329515.3		c.97G>C	p.Asp33His	missense	Exon 4 of 6	NP_001316444.1
	ZNF420	NM_001329516.3		c.97G>C	p.Asp33His	missense	Exon 3 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.97G>C	p.Asp33His	missense	Exon 4 of 5	ENSP00000338770.2	Q8TAQ5-1
	ZNF420	ENST00000876809.1		c.97G>C	p.Asp33His	missense	Exon 4 of 5	ENSP00000546868.1
	ZNF420	ENST00000876810.1		c.97G>C	p.Asp33His	missense	Exon 5 of 6	ENSP00000546869.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 244008 AF XY: 0.00

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453958 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722608

African (AFR) AF: 0.0000906 AC: 3 AN: 33102

American (AMR) AF: 0.00 AC: 0 AN: 43492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 83390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109406

Other (OTH) AF: 0.00 AC: 0 AN: 60062

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.0000482 AC: 2 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000824 AC: 1

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.60		Loss of helix (P = 0.0093)
MVP		0.49
MPC		1.2
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.50
gMVP		0.17
Mutation Taster		=91/9	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: rs747659700; hg19: chr19-37581984;