Variant 19-21182944-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_133473.4(ZNF431):c.641G>T(p.Cys214Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,614,028 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0051 ( 24 hom. )

Consequence

ZNF431
NM_133473.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.267

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005800724).

BP6

Variant 19-21182944-G-T is Benign according to our data. Variant chr19-21182944-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1338686.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF431	NM_133473.4 linkuse as main transcript	c.641G>T	p.Cys214Phe	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.641G>T	p.Cys214Phe	missense_variant	5/5	1	NM_133473.4	P1
ZNF431	ENST00000598331.1 linkuse as main transcript	c.761G>T	p.Cys254Phe	missense_variant	6/6	5
ZNF431	ENST00000600692.5 linkuse as main transcript	c.*228G>T		3_prime_UTR_variant	6/6	5
ZNF431	ENST00000594425.5 linkuse as main transcript	c.97-6921G>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

556

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00482

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00436

AC:

1091

AN:

250306

Hom.:

AF XY:

0.00424

AC XY:

575

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.000443

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00150

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.00461

Gnomad OTH exome

AF:

0.00675

GnomAD4 exome

AF:

0.00511

AC:

7470

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

3677

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.0163

Gnomad4 NFE exome

AF:

0.00544

Gnomad4 OTH exome

AF:

0.00389

GnomAD4 genome

AF:

0.00366

AC:

557

AN:

152280

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.00482

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00362

Hom.:

Bravo

AF:

0.00264

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00489

AC:

ExAC

AF:

0.00394

AC:

478

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

Cadd

Benign

4.3

Dann

Benign

0.65

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.061

T;T

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.025

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-8.4

D;.

REVEL

Benign

0.059

Sift

Benign

0.26

T;.

Sift4G

Benign

0.70

T;T

Polyphen

0.058

B;.

Vest4

0.095

MVP

0.072

MPC

0.62

ClinPred

0.017

GERP RS

-1.6

Varity_R

0.17

gMVP

0.0083

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