NM_001001415.4:c.503C>A

Variant names:

• chr19-21536556-C-A
• rs202041854
• NM_001001415.4:c.503C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001415.4(ZNF429):​c.503C>A​(p.Thr168Asn) 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. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T168I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF429 NM_001001415.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 1 publications found

Genes affected

ZNF429 (HGNC:20817): (zinc finger protein 429) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15683648).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001415.4. 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
	ZNF429	NM_001001415.4	MANE Select	c.503C>A	p.Thr168Asn	missense	Exon 4 of 4	NP_001001415.2	Q86V71
	ZNF429	NM_001346912.2		c.497C>A	p.Thr166Asn	missense	Exon 4 of 4	NP_001333841.1
	ZNF429	NM_001346913.2		c.407C>A	p.Thr136Asn	missense	Exon 5 of 5	NP_001333842.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF429	ENST00000358491.9	TSL:3 MANE Select	c.503C>A	p.Thr168Asn	missense	Exon 4 of 4	ENSP00000351280.3	Q86V71
	ZNF429	ENST00000597078.5	TSL:1	c.227-5208C>A		intron	N/A	ENSP00000470300.1	M0QZ47
	ZNF429	ENST00000967842.1		c.464C>A	p.Thr155Asn	missense	Exon 4 of 4	ENSP00000637901.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.4
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.034
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.35		Loss of phosphorylation at T168 (P = 0.0304)
MVP		0.32
MPC		0.21
ClinPred		0.49	T
GERP RS		-0.85
Varity_R		0.25
gMVP		0.037
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: rs202041854; hg19: chr19-21719358;