rs774815839

Positions:

• chr3-43080573-C-G
• chr3-43080573-C-T

Variant summary

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

The NM_032806.6(POMGNT2):​c.859G>C​(p.Glu287Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E287K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: POMGNT2 NM_032806.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92

Genes affected

POMGNT2 (HGNC:25902): (protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-)) This gene encodes a protein with glycosyltransferase activity although its function is not currently known. [provided by RefSeq, Sep 2012]

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=0.16965225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT2	NM_032806.6	c.859G>C	p.Glu287Gln	missense_variant	2/2	ENST00000344697.3
POMGNT2	XM_005265515.4	c.859G>C	p.Glu287Gln	missense_variant	3/3
POMGNT2	XM_011534163.3	c.859G>C	p.Glu287Gln	missense_variant	3/3
POMGNT2	XM_017007353.2	c.859G>C	p.Glu287Gln	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT2	ENST00000344697.3	c.859G>C	p.Glu287Gln	missense_variant	2/2	1	NM_032806.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	0.019
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.93	D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.63	N;N
REVEL	Benign	0.22
Sift	Benign	0.054	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0020	B;B
Vest4		0.15
MutPred		0.53		Gain of glycosylation at Y288 (P = 0.0514);Gain of glycosylation at Y288 (P = 0.0514);
MVP		0.70
MPC		0.51
ClinPred		0.41	T
GERP RS		5.5
Varity_R		0.12
gMVP		0.53

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: rs774815839; hg19: chr3-43122065;