Variant 16-89954337-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001242818.2(DEF8):c.85C>G(p.Gln29Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00538 in 1,613,846 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 226 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 186 hom. )

Consequence

DEF8
NM_001242818.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.77

Variant links:

Genes affected

DEF8 (HGNC:25969): (differentially expressed in FDCP 8 homolog) Predicted to enable metal ion binding activity. Predicted to be involved in lysosome localization; positive regulation of bone resorption; and positive regulation of ruffle assembly. [provided by Alliance of Genome Resources, Apr 2022]

DEF8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017540157).

BP6

Variant 16-89954337-C-G is Benign according to our data. Variant chr16-89954337-C-G is described in ClinVar as [Benign]. Clinvar id is 768807.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.099 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEF8	NM_001242818.2 linkuse as main transcript	c.85C>G	p.Gln29Glu	missense_variant	3/13	ENST00000563594.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEF8	ENST00000563594.6 linkuse as main transcript	c.85C>G	p.Gln29Glu	missense_variant	3/13	1	NM_001242818.2	P1	Q6ZN54-5

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4445

AN:

152100

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00734

AC:

1839

AN:

250536

Hom.:

AF XY:

0.00525

AC XY:

712

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00289

AC:

4224

AN:

1461628

Hom.:

186

Cov.:

AF XY:

0.00241

AC XY:

1751

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.00472

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000836

Gnomad4 OTH exome

AF:

0.00629

GnomAD4 genome

AF:

0.0292

AC:

4451

AN:

152218

Hom.:

226

Cov.:

AF XY:

0.0284

AC XY:

2117

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00862

Hom.:

Bravo

AF:

0.0337

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.101

AC:

442

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00897

AC:

1089

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.0091

FATHMM_MKL

Uncertain

0.93

MetaRNN

Benign

0.0018

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.38

N;N;.;.;N;N;N;N;N;N;N;N;N;N;N;N;D

Sift

Benign

0.10

T;T;.;.;T;T;T;T;T;T;T;T;T;T;T;T;D

Sift4G

Benign

0.32

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.034

B;.;B;B;.;.;.;.;B;B;.;.;B;.;B;.;.

Vest4

0.31

MVP

0.17

MPC

0.052

ClinPred

0.013

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.079

gMVP

0.080

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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