Variant 19-21183294-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_133473.4(ZNF431):c.991C>T(p.Leu331Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZNF431
NM_133473.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.389

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF431	NM_133473.4 linkuse as main transcript	c.991C>T	p.Leu331Phe	missense_variant	5/5	ENST00000311048.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF431	ENST00000311048.11 linkuse as main transcript	c.991C>T	p.Leu331Phe	missense_variant	5/5	1	NM_133473.4	P1
ZNF431	ENST00000600692.5 linkuse as main transcript	c.*578C>T		3_prime_UTR_variant	6/6	5
ZNF431	ENST00000594425.5 linkuse as main transcript	c.97-6571C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250302

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

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:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.0000297

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.991C>T (p.L331F) alteration is located in exon 5 (coding exon 5) of the ZNF431 gene. This alteration results from a C to T substitution at nucleotide position 991, causing the leucine (L) at amino acid position 331 to be replaced by a phenylalanine (F). 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

0.30

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.42

M_CAP

Benign

0.0083

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.83

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.080

Sift

Benign

0.059

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.15

MutPred

0.75

Loss of helix (P = 0.1299);

MVP

0.52

MPC

0.52

ClinPred

0.60

GERP RS

1.0

Varity_R

0.11

gMVP

0.026

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