Variant chr16-2831905-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000382280.8(ZG16B):c.265G>A(p.Ala89Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,614,096 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

ZG16B
ENST00000382280.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

ZG16B (HGNC:30456): (zymogen granule protein 16B) Predicted to enable carbohydrate binding activity. Involved in retina homeostasis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ZG16B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0080084205).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZG16B	NM_145252.3 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	4/4	ENST00000382280.8	NP_660295.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZG16B	ENST00000382280.8 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	4/4	1	NM_145252.3	ENSP00000371715	P1
ZG16B	ENST00000572863.2 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	3/3	2		ENSP00000461740	P1
ZG16B	ENST00000570670.6 linkuse as main transcript	c.155+1109G>A		intron_variant		3		ENSP00000460793
ZG16B	ENST00000573019.1 linkuse as main transcript	n.517G>A		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000329

AC:

AN:

249562

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00189

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000177

AC:

259

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

123

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.00121

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000453

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000186

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.000503

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000289

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.373G>A (p.A125T) alteration is located in exon 4 (coding exon 4) of the ZG16B gene. This alteration results from a G to A substitution at nucleotide position 373, causing the alanine (A) at amino acid position 125 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.058

DANN

Benign

0.70

DEOGEN2

Benign

0.0042

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0036

M_CAP

Benign

0.0014

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.33

N;.

REVEL

Benign

0.013

Sift

Benign

0.55

T;.

Sift4G

Benign

0.58

T;T

Polyphen

0.24

B;.

Vest4

0.013

MVP

0.014

MPC

0.024

ClinPred

0.0030

GERP RS

-5.9

Varity_R

0.28

gMVP

0.041

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