Genetic Variant ZG16B:c.-12C>T (chr16-2830430-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145252.3(ZG16B):c.-12C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000767 in 1,603,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

ZG16B
NM_145252.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.223

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102988005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZG16B	NM_145252.3 link	c.-12C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	ENST00000382280.8	NP_660295.3	Q96DA0G8H6I3
ZG16B	NM_145252.3 link	c.-12C>T		5_prime_UTR_variant	Exon 2 of 4	ENST00000382280.8	NP_660295.3	Q96DA0G8H6I3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZG16B	ENST00000382280 link	c.-12C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	1	NM_145252.3	ENSP00000371715.4		Q96DA0
ZG16B	ENST00000382280 link	c.-12C>T		5_prime_UTR_variant	Exon 2 of 4	1	NM_145252.3	ENSP00000371715.4		Q96DA0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000265

AC:

AN:

226436

Hom.:

AF XY:

0.0000162

AC XY:

AN XY:

123390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000608

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000395

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.0000820

AC:

119

AN:

1450918

Hom.:

Cov.:

AF XY:

0.0000791

AC XY:

AN XY:

721062

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000984

Gnomad4 OTH exome

AF:

0.0000835

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.97C>T (p.R33W) alteration is located in exon 2 (coding exon 2) of the ZG16B gene. This alteration results from a C to T substitution at nucleotide position 97, causing the arginine (R) at amino acid position 33 to be replaced by a tryptophan (W). 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

Benign

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.36

CADD

Benign

9.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.039

M_CAP

Benign

0.012

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.97

N;.

REVEL

Benign

0.086

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;.

Vest4

0.20

MutPred

0.27

Loss of disorder (P = 0.0061);.;

MVP

0.13

MPC

0.14

ClinPred

0.36

GERP RS

0.49

Varity_R

0.067

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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