Variant 16-88427474-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001367624.2(ZNF469):c.4C>A(p.Pro2Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000735 in 1,360,718 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ZNF469
NM_001367624.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

ZNF469 (HGNC:23216): (zinc finger protein 469) This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome. [provided by RefSeq, Jul 2008]

ZNF469 links:

LOC112268182 (HGNC:):

LOC112268182 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
ZNF469	NM_001367624.2 linkuse as main transcript	c.4C>A	p.Pro2Thr	missense_variant	3/3	ENST00000565624.3
LOC112268182	XR_007065178.1 linkuse as main transcript	n.251-1208G>T		intron_variant, non_coding_transcript_variant
ZNF469	XM_047434810.1 linkuse as main transcript	c.4C>A	p.Pro2Thr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF469	ENST00000565624.3 linkuse as main transcript	c.4C>A	p.Pro2Thr	missense_variant	3/3		NM_001367624.2	A2
ZNF469	ENST00000437464.1 linkuse as main transcript	c.4C>A	p.Pro2Thr	missense_variant	1/2	5		P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1360718

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668742

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:

9.39e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jul 25, 2023

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2 of the ZNF469 protein (p.Pro2Thr). This variant is not present in population databases (gnomAD no frequency). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

0.087

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.52

T;.

M_CAP

Pathogenic

0.38

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.7

D;D

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.41

MutPred

0.22

Gain of phosphorylation at P2 (P = 0.0066);Gain of phosphorylation at P2 (P = 0.0066);

MVP

0.41

ClinPred

0.89

GERP RS

3.8

gMVP

0.13

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over