Variant 19-21183324-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000311048.11(ZNF431):c.1021G>A(p.Glu341Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF431
ENST00000311048.11 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.868

Variant links:

Genes affected

ZNF431 (HGNC:20809): (zinc finger protein 431) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein may negatively regulate transcription of target genes, including the hedgehog signaling pathway receptor patched 1, by interacting with histone deacetylases. Mutations in this gene may be associated with non-syndromic facial clefting in human patients. [provided by RefSeq, Jul 2016]

ZNF431 links:

ZNF431 (HGNC:):

ZNF431 links:

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ACMG classification

Classification made for transcript

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=0.2057825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF431	NM_133473.4 linkuse as main transcript	c.1021G>A	p.Glu341Lys	missense_variant	5/5	ENST00000311048.11	NP_597730.2	Q8TF32A0A024R7Q8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF431	ENST00000311048.11 linkuse as main transcript	c.1021G>A	p.Glu341Lys	missense_variant	5/5	1	NM_133473.4	ENSP00000308578.6	Q8TF32
ZNF431	ENST00000600692.5 linkuse as main transcript	c.*608G>A		3_prime_UTR_variant	6/6	5		ENSP00000470668.1	M0QZN7
ZNF431	ENST00000594425.5 linkuse as main transcript	c.97-6541G>A		intron_variant		2		ENSP00000469460.1	M0QXY3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250368

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Malignant tumor of prostate

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

0.15

Eigen_PC

Benign

-0.019

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.21

M_CAP

Benign

0.0057

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.97

MutationTaster

Benign

0.89

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.095

Sift

Benign

0.054

Sift4G

Benign

0.069

Polyphen

1.0

Vest4

0.18

MutPred

0.51

Gain of methylation at E341 (P = 0.0051);

MVP

0.21

MPC

0.53

ClinPred

0.88

GERP RS

1.0

Varity_R

0.17

gMVP

0.021

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over