16-88431120-C-T

Position:

chr16-88431120-C-T

Variant summary

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

The NM_001367624.2(ZNF469):c.3650C>T(p.Pro1217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,550,268 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 96 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 94 hom. )

Consequence

ZNF469
NM_001367624.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.11

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=0.0022440255).

BP6

Variant 16-88431120-C-T is Benign according to our data. Variant chr16-88431120-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 235813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF469	NM_001367624.2 linkuse as main transcript	c.3650C>T	p.Pro1217Leu	missense_variant	3/3	ENST00000565624.3	NP_001354553.1
ZNF469	XM_047434810.1 linkuse as main transcript	c.3650C>T	p.Pro1217Leu	missense_variant	4/4		XP_047290766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF469	ENST00000565624.3 linkuse as main transcript	c.3650C>T	p.Pro1217Leu	missense_variant	3/3	6	NM_001367624.2	ENSP00000456500.2		H3BS19
ZNF469	ENST00000437464.1 linkuse as main transcript	c.3566C>T	p.Pro1189Leu	missense_variant	2/2	5		ENSP00000402343.1		Q96JG9

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2958

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00429

AC:

656

AN:

152964

Hom.:

AF XY:

0.00317

AC XY:

258

AN XY:

81434

show subpopulations

Gnomad AFR exome

AF:

0.0702

Gnomad AMR exome

AF:

0.00397

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000918

Gnomad SAS exome

AF:

0.000395

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000340

Gnomad OTH exome

AF:

0.000462

GnomAD4 exome

AF:

0.00203

AC:

2838

AN:

1398040

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1188

AN XY:

689518

show subpopulations

Gnomad4 AFR exome

AF:

0.0737

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.000265

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000417

Gnomad4 OTH exome

AF:

0.00481

GnomAD4 genome

AF:

0.0194

AC:

2960

AN:

152228

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1367

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0676

Gnomad4 AMR

AF:

0.00752

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00608

Hom.:

Bravo

AF:

0.0228

ExAC

AF:

0.00820

AC:

187

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 04, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Brittle cornea syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 30, 2016

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

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 08, 2019

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

0.10

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.55

T;.

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.062

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.0030

D;D

Vest4

0.12

MVP

0.33

ClinPred

0.012

GERP RS

3.2

gMVP

0.035

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