19-52034081-C-T

Variant names:

• chr19-52034081-C-T
• rs117633649
• NM_014650.4:c.1598G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014650.4(ZNF432):​c.1598G>A​(p.Arg533Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00887 in 1,614,160 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (14 hom., cov: 33)
  • Exomes 𝑓: 0.0090 (84 hom.)
• Consequence: ZNF432 NM_014650.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13
• Publications: 9 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055719614).
• BP6: Variant 19-52034081-C-T is Benign according to our data. Variant chr19-52034081-C-T is described in ClinVar as Benign. ClinVar VariationId is 777533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.1598G>A	p.Arg533Gln	missense	Exon 5 of 5	NP_055465.1	O94892
	ZNF432	NM_001322284.2		c.1598G>A	p.Arg533Gln	missense	Exon 5 of 5	NP_001309213.1	O94892
	ZNF432	NM_001322285.1		c.1598G>A	p.Arg533Gln	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.1598G>A	p.Arg533Gln	missense	Exon 5 of 5	ENSP00000221315.4	O94892
	ZNF432	ENST00000594154.5	TSL:1	c.1598G>A	p.Arg533Gln	missense	Exon 5 of 5	ENSP00000470488.1	O94892
	ZNF432	ENST00000913743.1		c.1598G>A	p.Arg533Gln	missense	Exon 5 of 5	ENSP00000583802.1

Frequencies

GnomAD3 genomes AF: 0.00792 AC: 1206 AN: 152208 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00923

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00802 AC: 2016 AN: 251364 AF XY: 0.00801

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00757

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0192

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.00896 AC: 13104 AN: 1461834 Hom.: 84 Cov.: 30 AF XY: 0.00888 AC XY: 6458 AN XY: 727212

African (AFR) AF: 0.00158 AC: 53 AN: 33480

American (AMR) AF: 0.00830 AC: 371 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00134 AC: 35 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.000800 AC: 69 AN: 86256

European-Finnish (FIN) AF: 0.0201 AC: 1073 AN: 53410

Middle Eastern (MID) AF: 0.0113 AC: 65 AN: 5764

European-Non Finnish (NFE) AF: 0.00979 AC: 10891 AN: 1111978

Other (OTH) AF: 0.00902 AC: 545 AN: 60396

GnomAD4 genome AF: 0.00792 AC: 1206 AN: 152326 Hom.: 14 Cov.: 33 AF XY: 0.00858 AC XY: 639 AN XY: 74484

African (AFR) AF: 0.00190 AC: 79 AN: 41580

American (AMR) AF: 0.0160 AC: 245 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.0201 AC: 213 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00923 AC: 628 AN: 68030

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00875 Hom.: 30

Bravo AF: 0.00771

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.0125 AC: 48

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.0119 AC: 102

ExAC AF: 0.00744 AC: 903

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0119

EpiControl AF: 0.0110

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.061
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.1
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.12
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.027	D
Polyphen		0.99	D
Vest4		0.18
MVP		0.30
MPC		0.31
ClinPred		0.036	T
GERP RS		2.8
Varity_R		0.28
gMVP		0.066
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: rs117633649; hg19: chr19-52537334; COSMIC: COSV55416167; COSMIC: COSV55416167;