rs149765326

Variant names:

• chr19-52034184-C-G
• NM_014650.4:c.1495G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-52034184-C-G
• chr19-52034184-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014650.4(ZNF432):​c.1495G>C​(p.Gly499Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF432 NM_014650.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2247149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF432	NM_014650.4	c.1495G>C	p.Gly499Arg	missense_variant	Exon 5 of 5	ENST00000221315.10	NP_055465.1
ZNF432	NM_001322284.2	c.1495G>C	p.Gly499Arg	missense_variant	Exon 5 of 5		NP_001309213.1
ZNF432	NM_001322285.1	c.1495G>C	p.Gly499Arg	missense_variant	Exon 5 of 5		NP_001309214.1
ZNF432	XM_024451806.2	c.1207G>C	p.Gly403Arg	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.1495G>C	p.Gly499Arg	missense_variant	Exon 5 of 5	1	NM_014650.4	ENSP00000221315.4
ZNF432	ENST00000594154.5	c.1495G>C	p.Gly499Arg	missense_variant	Exon 5 of 5	1		ENSP00000470488.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461818 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.00033	N
LIST_S2	Benign	0.61	.;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.14	N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.13
Sift	Benign	0.27	.;T
Sift4G	Benign	0.64	T;T
Polyphen		0.98	D;D
Vest4		0.34
MutPred		0.31		Gain of MoRF binding (P = 0.0272);Gain of MoRF binding (P = 0.0272);
MVP		0.29
MPC		0.29
ClinPred		0.37	T
GERP RS		1.6
Varity_R		0.070
gMVP		0.067

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: chr19-52537437;