16-29779316-A-G

Position:

• chr16-29779316-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000400752.6(ZG16):​c.50A>G​(p.Asn17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,392 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: 7.2e-7 (0 hom.)
• Consequence: ZG16 ENST00000400752.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.801

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028645158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZG16	NM_152338.4	c.50A>G	p.Asn17Ser	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	c.50A>G	p.Asn17Ser	missense_variant	2/4	1	NM_152338.4	ENSP00000383563	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385392 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 683610

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2024

The c.50A>G (p.N17S) alteration is located in exon 2 (coding exon 1) of the ZG16 gene. This alteration results from a A to G substitution at nucleotide position 50, causing the asparagine (N) at amino acid position 17 to be replaced by a serine (S). 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	0.055
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.025
DANN	Benign	0.80
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.054	N
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.026
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.082
MutPred		0.26		Gain of glycosylation at N17 (P = 0.0079);
MVP		0.030
ClinPred		0.046	T
GERP RS		-5.4
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29790637;