16-2830742-A-G

Variant names:

• chr16-2830742-A-G
• NM_145252.3:c.101A>G

Variant summary

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

The NM_145252.3(ZG16B):​c.101A>G​(p.Tyr34Cys) 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. 15/21 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: -1.12

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=0.08398867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZG16B	NM_145252.3	c.101A>G	p.Tyr34Cys	missense_variant	Exon 3 of 4	ENST00000382280.8	NP_660295.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZG16B	ENST00000382280.8	c.101A>G	p.Tyr34Cys	missense_variant	Exon 3 of 4	1	NM_145252.3	ENSP00000371715.4

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

Aug 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.209A>G (p.Y70C) alteration is located in exon 3 (coding exon 3) of the ZG16B gene. This alteration results from a A to G substitution at nucleotide position 209, causing the tyrosine (Y) at amino acid position 70 to be replaced by a cysteine (C). 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	0.31
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.8
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0061	N
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.085
Sift	Benign	0.13	T;.
Sift4G	Benign	0.18	T;T
Polyphen		1.0	D;.
Vest4		0.093
MutPred		0.38		Loss of sheet (P = 0.0037);.;
MVP		0.048
MPC		0.15
ClinPred		0.22	T
GERP RS		-1.3
Varity_R		0.32
gMVP		0.084

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-2880743;