Variant chr16-29779279-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000400752.6(ZG16):c.13G>A(p.Ala5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000722 in 1,385,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

ZG16
ENST00000400752.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.365

Variant links:

Genes affected

ZG16 (HGNC:30961): (zymogen granule protein 16) Predicted to enable carbohydrate binding activity and peptidoglycan binding activity. Predicted to be involved in protein transport. Predicted to act upstream of or within defense response to Gram-positive bacterium and suppression of symbiont entry into host. Located in Golgi lumen and collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ZG16 links:

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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=0.1380507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZG16	NM_152338.4 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	2/4	ENST00000400752.6	NP_689551.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZG16	ENST00000400752.6 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	2/4	1	NM_152338.4	ENSP00000383563	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

146280

Hom.:

AF XY:

0.0000129

AC XY:

AN XY:

77732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000941

Gnomad SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000331

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000722

AC:

AN:

1385476

Hom.:

Cov.:

AF XY:

0.00000731

AC XY:

AN XY:

683650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Feb 27, 2024

The c.13G>A (p.A5T) alteration is located in exon 2 (coding exon 1) of the ZG16 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the alanine (A) at amino acid position 5 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

Benign

0.093

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.1

DANN

Benign

0.97

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.041

M_CAP

Benign

0.0085

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.37

REVEL

Benign

0.084

Sift

Benign

0.095

Sift4G

Benign

0.29

Vest4

0.20

MutPred

0.36

Gain of disorder (P = 0.1464);

MVP

0.19

ClinPred

0.041

GERP RS

4.3

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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