Variant 16-88427475-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_001367624.2(ZNF469):c.5C>T(p.Pro2Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000294 in 1,361,566 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000029 ( 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	Protein
ZNF469	NM_001367624.2 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	3/3	ENST00000565624.3	NP_001354553.1
ZNF469	XM_047434810.1 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	4/4		XP_047290766.1
LOC112268182	XR_007065178.1 linkuse as main transcript	n.251-1209G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF469	ENST00000565624.3 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	3/3	6	NM_001367624.2	ENSP00000456500.2		H3BS19
ZNF469	ENST00000437464.1 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	1/2	5		ENSP00000402343.1		Q96JG9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000853

AC:

AN:

117242

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63818

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:

0.0000234

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000294

AC:

AN:

1361566

Hom.:

Cov.:

AF XY:

0.00000299

AC XY:

AN XY:

669230

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:

0.00000375

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

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2021

The p.P2L variant (also known as c.5C>T), located in coding exon 1 of the ZNF469 gene, results from a C to T substitution at nucleotide position 5. The proline at codon 2 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, leucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.089

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.60

T;.

M_CAP

Pathogenic

0.49

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.44

MutPred

0.19

Gain of stability (P = 0.0053);Gain of stability (P = 0.0053);

MVP

0.53

ClinPred

0.84

GERP RS

3.8

gMVP

0.10

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