19-52034249-C-G

Variant names:

• chr19-52034249-C-G
• NM_014650.4:c.1430G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014650.4(ZNF432):​c.1430G>C​(p.Arg477Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R477Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF432 NM_014650.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF432	NM_014650.4	c.1430G>C	p.Arg477Pro	missense_variant	Exon 5 of 5	ENST00000221315.10	NP_055465.1
ZNF432	NM_001322284.2	c.1430G>C	p.Arg477Pro	missense_variant	Exon 5 of 5		NP_001309213.1
ZNF432	NM_001322285.1	c.1430G>C	p.Arg477Pro	missense_variant	Exon 5 of 5		NP_001309214.1
ZNF432	XM_024451806.2	c.1142G>C	p.Arg381Pro	missense_variant	Exon 2 of 2		XP_024307574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF432	ENST00000221315.10	c.1430G>C	p.Arg477Pro	missense_variant	Exon 5 of 5	1	NM_014650.4	ENSP00000221315.4
ZNF432	ENST00000594154.5	c.1430G>C	p.Arg477Pro	missense_variant	Exon 5 of 5	1		ENSP00000470488.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461816 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.039
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.075	.;T
M_CAP	Benign	0.0026	T
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.2	.;D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.42
MutPred		0.67		Loss of MoRF binding (P = 0.0234);Loss of MoRF binding (P = 0.0234);
MVP		0.40
MPC		0.34
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.81
gMVP		0.30

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-52537502;