Genetic Variant NM_001308348.2:c.1421C>T (chr19-12015437-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001308348.2(ZNF433):c.1421C>T(p.Pro474Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,772 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF433
NM_001308348.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

Publications

0 publications found

Variant links:

Genes affected

ZNF433 (HGNC:20811): (zinc finger protein 433) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF433 links:

ENSG00000286098 (HGNC:):

ENSG00000286098 links:

ZNF433-AS1 (HGNC:53776): (ZNF433 and ZNF878 antisense RNA 1)

ZNF433-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18063772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF433	NM_001308348.2	MANE Select	c.1421C>T	p.Pro474Leu	missense	Exon 4 of 4	NP_001295277.1	F8VTV7
ZNF433	NM_001080411.3		c.1430C>T	p.Pro477Leu	missense	Exon 4 of 4	NP_001073880.1	Q8N7K0-1
ZNF433	NM_001308346.2		c.1427C>T	p.Pro476Leu	missense	Exon 5 of 5	NP_001295275.1	F8W0C9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF433	ENST00000550507.7	TSL:2 MANE Select	c.1421C>T	p.Pro474Leu	missense	Exon 4 of 4	ENSP00000448099.2	F8VTV7
ZNF433	ENST00000478765.6	TSL:1	c.1463C>T	p.Pro488Leu	missense	Exon 3 of 3	ENSP00000447951.2	C9JQA6
ZNF433	ENST00000419886.7	TSL:1	c.1325C>T	p.Pro442Leu	missense	Exon 5 of 5	ENSP00000393416.2	Q8N7K0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000360

AC:

AN:

249866

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.000554

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111930

Other (OTH)

AF:

0.0000331

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.28

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.38

M_CAP

Benign

0.0033

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

1.8

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-8.5

REVEL

Benign

0.14

Sift

Benign

0.030

Sift4G

Uncertain

0.026

Polyphen

1.0

Vest4

0.21

MutPred

0.44

Loss of ubiquitination at K476 (P = 0.0446)

MVP

0.32

MPC

0.058

ClinPred

0.36

GERP RS

0.13

Varity_R

0.11

gMVP

0.014

Mutation Taster

=97/3

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