19-52034033-C-T

Variant names:

• chr19-52034033-C-T
• rs780216788
• NM_014650.4:c.1646G>A

Variant summary

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

The NM_014650.4(ZNF432):​c.1646G>A​(p.Gly549Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,854 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZNF432 NM_014650.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.198
• Publications: 0 publications found

Genes affected

ZNF432 (HGNC:20810): (zinc finger protein 432) 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. Located in nucleoplasm. [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=0.14371458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014650.4. 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
	ZNF432	NM_014650.4	MANE Select	c.1646G>A	p.Gly549Asp	missense	Exon 5 of 5	NP_055465.1	O94892
	ZNF432	NM_001322284.2		c.1646G>A	p.Gly549Asp	missense	Exon 5 of 5	NP_001309213.1	O94892
	ZNF432	NM_001322285.1		c.1646G>A	p.Gly549Asp	missense	Exon 5 of 5	NP_001309214.1	O94892

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF432	ENST00000221315.10	TSL:1 MANE Select	c.1646G>A	p.Gly549Asp	missense	Exon 5 of 5	ENSP00000221315.4	O94892
	ZNF432	ENST00000594154.5	TSL:1	c.1646G>A	p.Gly549Asp	missense	Exon 5 of 5	ENSP00000470488.1	O94892
	ZNF432	ENST00000913743.1		c.1646G>A	p.Gly549Asp	missense	Exon 5 of 5	ENSP00000583802.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461854 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

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: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

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	Pathogenic	0.80
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.20
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.086
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.098	T
Polyphen		0.41	B
Vest4		0.45
MutPred		0.59		Gain of ubiquitination at K553 (P = 0.0539)
MVP		0.25
MPC		0.33
ClinPred		0.72	D
GERP RS		1.6
Varity_R		0.47
gMVP		0.090
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

dbSNP: rs780216788; hg19: chr19-52537286;