16-2830720-T-C

Position:

• chr16-2830720-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145252.3(ZG16B):​c.79T>C​(p.Tyr27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ZG16B NM_145252.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.578

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]

ACMG classification

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=0.08406025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZG16B	NM_145252.3	c.79T>C	p.Tyr27His	missense_variant	3/4	ENST00000382280.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZG16B	ENST00000382280.8	c.79T>C	p.Tyr27His	missense_variant	3/4	1	NM_145252.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jul 25, 2023

The c.187T>C (p.Y63H) alteration is located in exon 3 (coding exon 3) of the ZG16B gene. This alteration results from a T to C substitution at nucleotide position 187, causing the tyrosine (Y) at amino acid position 63 to be replaced by a histidine (H). 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.5
DANN	Benign	0.66
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.018
Sift	Benign	0.18	T;.
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.41	B;.
Vest4		0.18
MutPred		0.37		Loss of sheet (P = 0.0025);.;
MVP		0.014
MPC		0.062
ClinPred		0.18	T
GERP RS		-1.5
Varity_R		0.20
gMVP		0.16

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

Other links and lift over

dbSNP: rs868622753; hg19: chr16-2880721;