16-88438442-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367624.2(ZNF469):c.10972G>C(p.Glu3658Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,549,886 control chromosomes in the GnomAD database, including 134,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E3658?) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.43 ( 14845 hom., cov: 34)

Exomes 𝑓: 0.41 ( 119536 hom. )

Consequence

ZNF469
NM_001367624.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0480

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.0975698E-5).

BP6

Variant 16-88438442-G-C is Benign according to our data. Variant chr16-88438442-G-C is described in ClinVar as [Benign]. Clinvar id is 321020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88438442-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF469	NM_001367624.2 link	c.10972G>C	p.Glu3658Gln	missense_variant	Exon 3 of 3	ENST00000565624.3	NP_001354553.1
ZNF469	XM_047434810.1 link	c.10972G>C	p.Glu3658Gln	missense_variant	Exon 4 of 4		XP_047290766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF469	ENST00000565624.3 link	c.10972G>C	p.Glu3658Gln	missense_variant	Exon 3 of 3	6	NM_001367624.2	ENSP00000456500.2		H3BS19
ZNF469	ENST00000437464.1 link	c.10888G>C	p.Glu3630Gln	missense_variant	Exon 2 of 2	5		ENSP00000402343.1		Q96JG9

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66044

AN:

151960

Hom.:

14804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.536

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.459

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.359

GnomAD3 exomes

AF:

0.373

AC:

54523

AN:

146310

Hom.:

10749

AF XY:

0.364

AC XY:

28626

AN XY:

78620

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.318

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.420

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.415

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.409

AC:

571778

AN:

1397808

Hom.:

119536

Cov.:

AF XY:

0.404

AC XY:

278240

AN XY:

689390

show subpopulations

Gnomad4 AFR exome

AF:

0.530

Gnomad4 AMR exome

AF:

0.323

Gnomad4 ASJ exome

AF:

0.295

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.455

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.381

GnomAD4 genome

AF:

0.435

AC:

66134

AN:

152078

Hom.:

14845

Cov.:

AF XY:

0.432

AC XY:

32069

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.355

Gnomad4 ASJ

AF:

0.288

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.459

Gnomad4 NFE

AF:

0.419

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.408

Hom.:

4155

Bravo

AF:

0.429

TwinsUK

AF:

0.422

AC:

1566

ALSPAC

AF:

0.444

AC:

1710

ESP6500AA

AF:

0.533

AC:

729

ESP6500EA

AF:

0.415

AC:

1311

ExAC

AF:

0.315

AC:

6601

Asia WGS

AF:

0.328

AC:

1141

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brittle cornea syndrome 1

Benign:4

Jan 15, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Sep 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Cardiovascular phenotype

Benign:1

Dec 04, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.0074

T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.51

T;.

MetaRNN

Benign

0.000041

T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.040

Sift

Benign

0.043

D;D

Sift4G

Uncertain

0.022

D;D

Vest4

0.022

ClinPred

0.0025

GERP RS

1.3

gMVP

0.030

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