rs375879947

chr3-43080497-T-Achr3-43080497-T-C

Variant summary

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

The NM_032806.6(POMGNT2):c.935A>T(p.Gln312Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q312R) 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: 5.14

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT2	NM_032806.6	c.935A>T	p.Gln312Leu	missense_variant	2/2	ENST00000344697.3
POMGNT2	XM_005265515.4	c.935A>T	p.Gln312Leu	missense_variant	3/3
POMGNT2	XM_011534163.3	c.935A>T	p.Gln312Leu	missense_variant	3/3
POMGNT2	XM_017007353.2	c.935A>T	p.Gln312Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT2	ENST00000344697.3	c.935A>T	p.Gln312Leu	missense_variant	2/2	1	NM_032806.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727240

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;D
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.9	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		0.46	P;P
Vest4		0.70
MutPred		0.56		Gain of ubiquitination at K317 (P = 0.1434);Gain of ubiquitination at K317 (P = 0.1434);
MVP		0.65
MPC		0.67
ClinPred		0.95	D
GERP RS		3.4
Varity_R		0.36
gMVP		0.60

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: rs375879947; hg19: chr3-43121989;