Genetic Variant ZNF430:p.Pro106His (chr19-21034179-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025189.4(ZNF430):c.317C>A(p.Pro106His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P106L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF430
NM_025189.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.950

Publications

0 publications found

Variant links:

Genes affected

ZNF430 (HGNC:20808): (zinc finger protein 430) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in substantia nigra development. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF430 links:

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ACMG classification

Classification was made for transcript

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=0.09025219).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025189.4. 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
	ZNF430	NM_025189.4	MANE Select	c.317C>A	p.Pro106His	missense	Exon 4 of 5	NP_079465.3
	ZNF430	NM_001172671.2		c.314C>A	p.Pro105His	missense	Exon 4 of 5	NP_001166142.1	Q2NKJ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF430	ENST00000261560.10	TSL:1 MANE Select	c.317C>A	p.Pro106His	missense	Exon 4 of 5	ENSP00000261560.4	Q9H8G1
ZNF430	ENST00000935026.1		c.224C>A	p.Pro75His	missense	Exon 3 of 4	ENSP00000605085.1
ZNF430	ENST00000594110.5	TSL:4	c.317C>A	p.Pro106His	missense	Exon 4 of 5	ENSP00000473069.1	M0R392

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244476

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441672

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32846

American (AMR)

AF:

0.0000228

AC:

AN:

43782

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25464

East Asian (EAS)

AF:

0.00

AC:

AN:

39222

South Asian (SAS)

AF:

0.00

AC:

AN:

82874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100250

Other (OTH)

AF:

0.00

AC:

AN:

59364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.5

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.074

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.17

M_CAP

Benign

0.0010

MetaRNN

Benign

0.090

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.62

PhyloP100

-0.95

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-6.7

REVEL

Benign

0.044

Sift

Benign

0.30

Sift4G

Benign

0.45

Polyphen

0.054

Vest4

0.29

MutPred

0.43

Loss of phosphorylation at T109 (P = 0.1789)

MVP

0.061

MPC

0.17

ClinPred

0.31

GERP RS

0.20

Varity_R

0.17

gMVP

0.036

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over