3-43080438-C-A

Position:

• chr3-43080438-C-A

Variant summary

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

The ENST00000344697.3(POMGNT2):​c.994G>T​(p.Val332Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,872 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. V332M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POMGNT2 ENST00000344697.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00

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	Protein	UniProt
POMGNT2	NM_032806.6	c.994G>T	p.Val332Leu	missense_variant	2/2	ENST00000344697.3	NP_116195.2
POMGNT2	XM_005265515.4	c.994G>T	p.Val332Leu	missense_variant	3/3		XP_005265572.1
POMGNT2	XM_011534163.3	c.994G>T	p.Val332Leu	missense_variant	3/3		XP_011532465.1
POMGNT2	XM_017007353.2	c.994G>T	p.Val332Leu	missense_variant	4/4		XP_016862842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMGNT2	ENST00000344697.3	c.994G>T	p.Val332Leu	missense_variant	2/2	1	NM_032806.6	ENSP00000344125	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251254 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461872 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.47	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.13	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.90	P;P
Vest4		0.68
MutPred		0.34		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.81
MPC		0.85
ClinPred		0.67	D
GERP RS		5.6
Varity_R		0.093
gMVP		0.66

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: rs549430013; hg19: chr3-43121930;