chr19-52034498-G-A

Position:

• chr19-52034498-G-A

Variant summary

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

The NM_014650.4(ZNF432):​c.1181C>T​(p.Thr394Ile) 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. 14/21 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: -1.46

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=0.10935962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF432	NM_014650.4	c.1181C>T	p.Thr394Ile	missense_variant	5/5	ENST00000221315.10
ZNF432	NM_001322284.2	c.1181C>T	p.Thr394Ile	missense_variant	5/5
ZNF432	NM_001322285.1	c.1181C>T	p.Thr394Ile	missense_variant	5/5
ZNF432	XM_024451806.2	c.893C>T	p.Thr298Ile	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF432	ENST00000221315.10	c.1181C>T	p.Thr394Ile	missense_variant	5/5	1	NM_014650.4	P1
ZNF432	ENST00000594154.5	c.1181C>T	p.Thr394Ile	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.1181C>T (p.T394I) alteration is located in exon 5 (coding exon 4) of the ZNF432 gene. This alteration results from a C to T substitution at nucleotide position 1181, causing the threonine (T) at amino acid position 394 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.60
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.24	.;T
M_CAP	Benign	0.00036	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.2	.;D
REVEL	Benign	0.066
Sift	Benign	0.41	.;T
Sift4G	Benign	0.84	T;T
Polyphen		0.016	B;B
Vest4		0.12
MutPred		0.41		Loss of phosphorylation at T394 (P = 0.0321);Loss of phosphorylation at T394 (P = 0.0321);
MVP		0.12
MPC		0.045
ClinPred		0.052	T
GERP RS		-2.0
Varity_R		0.14
gMVP		0.030

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: chr19-52537751;