19-52033998-G-C

Variant names:

• chr19-52033998-G-C
• rs376379889
• NM_014650.4:c.1681C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014650.4(ZNF432):​c.1681C>G​(p.Gln561Glu) 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. 16/22 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: ZNF432 NM_014650.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.37
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05237481).

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.1681C>G	p.Gln561Glu	missense	Exon 5 of 5	NP_055465.1	O94892
	ZNF432	NM_001322284.2		c.1681C>G	p.Gln561Glu	missense	Exon 5 of 5	NP_001309213.1	O94892
	ZNF432	NM_001322285.1		c.1681C>G	p.Gln561Glu	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.1681C>G	p.Gln561Glu	missense	Exon 5 of 5	ENSP00000221315.4	O94892
	ZNF432	ENST00000594154.5	TSL:1	c.1681C>G	p.Gln561Glu	missense	Exon 5 of 5	ENSP00000470488.1	O94892
	ZNF432	ENST00000913743.1		c.1681C>G	p.Gln561Glu	missense	Exon 5 of 5	ENSP00000583802.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251336 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

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 Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

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	Benign	0.097
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.00072	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.65	N
PhyloP100		-1.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.043
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Polyphen		0.43	B
Vest4		0.14
MVP		0.18
MPC		0.045
ClinPred		0.050	T
GERP RS		0.42
Varity_R		0.18
gMVP		0.033
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: rs376379889; hg19: chr19-52537251;