19-52034184-C-T

Variant names:

• chr19-52034184-C-T
• rs149765326
• NM_014650.4:c.1495G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014650.4(ZNF432):​c.1495G>A​(p.Gly499Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,612,728 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: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ZNF432 NM_014650.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.69
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16934326).

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.1495G>A	p.Gly499Arg	missense	Exon 5 of 5	NP_055465.1	O94892
	ZNF432	NM_001322284.2		c.1495G>A	p.Gly499Arg	missense	Exon 5 of 5	NP_001309213.1	O94892
	ZNF432	NM_001322285.1		c.1495G>A	p.Gly499Arg	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.1495G>A	p.Gly499Arg	missense	Exon 5 of 5	ENSP00000221315.4	O94892
	ZNF432	ENST00000594154.5	TSL:1	c.1495G>A	p.Gly499Arg	missense	Exon 5 of 5	ENSP00000470488.1	O94892
	ZNF432	ENST00000913743.1		c.1495G>A	p.Gly499Arg	missense	Exon 5 of 5	ENSP00000583802.1

Frequencies

GnomAD3 genomes AF: 0.000113 AC: 17 AN: 150790 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000733

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000192

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000796 AC: 20 AN: 251340 AF XY: 0.0000589

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000118 AC: 173 AN: 1461818 Hom.: 0 Cov.: 30 AF XY: 0.0000976 AC XY: 71 AN XY: 727206

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86240

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

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

European-Non Finnish (NFE) AF: 0.000137 AC: 152 AN: 1111984

Other (OTH) AF: 0.000116 AC: 7 AN: 60394

GnomAD4 genome AF: 0.000119 AC: 18 AN: 150910 Hom.: 0 Cov.: 33 AF XY: 0.000109 AC XY: 8 AN XY: 73716

African (AFR) AF: 0.0000974 AC: 4 AN: 41060

American (AMR) AF: 0.00 AC: 0 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5060

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000192 AC: 13 AN: 67690

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000154 Hom.: 0

Bravo AF: 0.000117

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

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	0.91
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.00027	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.14	N
PhyloP100		-1.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.27	T
Sift4G	Benign	0.64	T
Polyphen		0.99	D
Vest4		0.34
MutPred		0.31		Gain of MoRF binding (P = 0.0272)
MVP		0.29
MPC		0.29
ClinPred		0.052	T
GERP RS		1.6
Varity_R		0.070
gMVP		0.067
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: rs149765326; hg19: chr19-52537437; COSMIC: COSV55416770; COSMIC: COSV55416770;