16-2831800-C-T

Variant names:

• chr16-2831800-C-T
• rs547452926
• NM_145252.3:c.160C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145252.3(ZG16B):​c.160C>T​(p.Gln54*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZG16B NM_145252.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145252.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZG16B	NM_145252.3	MANE Select	c.160C>T	p.Gln54*	stop_gained	Exon 4 of 4	NP_660295.3	Q96DA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZG16B	ENST00000382280.8	TSL:1 MANE Select	c.160C>T	p.Gln54*	stop_gained	Exon 4 of 4	ENSP00000371715.4	Q96DA0
	ZG16B	ENST00000572863.2	TSL:2	c.160C>T	p.Gln54*	stop_gained	Exon 3 of 3	ENSP00000461740.2	Q96DA0
	ZG16B	ENST00000902257.1		c.160C>T	p.Gln54*	stop_gained	Exon 4 of 4	ENSP00000572316.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458416 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725120

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5496

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109840

Other (OTH) AF: 0.00 AC: 0 AN: 60246

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.24	N
PhyloP100		0.40
Vest4		0.077
GERP RS		3.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 3

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

Other links and lift over

dbSNP: rs547452926; hg19: chr16-2881801;