rs115870061

Variant names:

• chr3-43080670-C-A
• rs115870061
• NM_032806.6:c.762G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-43080670-C-A
• chr3-43080670-C-T

Variant summary

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

The NM_032806.6(POMGNT2):​c.762G>T​(p.Lys254Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POMGNT2 NM_032806.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.250

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 rank	MANE	Protein	UniProt
POMGNT2	NM_032806.6	c.762G>T	p.Lys254Asn	missense_variant	Exon 2 of 2	ENST00000344697.3	NP_116195.2
POMGNT2	XM_005265515.4	c.762G>T	p.Lys254Asn	missense_variant	Exon 3 of 3		XP_005265572.1
POMGNT2	XM_011534163.3	c.762G>T	p.Lys254Asn	missense_variant	Exon 3 of 3		XP_011532465.1
POMGNT2	XM_017007353.2	c.762G>T	p.Lys254Asn	missense_variant	Exon 4 of 4		XP_016862842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT2	ENST00000344697.3	c.762G>T	p.Lys254Asn	missense_variant	Exon 2 of 2	1	NM_032806.6	ENSP00000344125.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461886 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Uncertain:1

Jun 27, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 540487). This variant has not been reported in the literature in individuals affected with POMGNT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 254 of the POMGNT2 protein (p.Lys254Asn). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.99	.;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.92	N;N
REVEL	Uncertain	0.39
Sift	Benign	0.048	D;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.87	P;P
Vest4		0.83
MutPred		0.47		Loss of ubiquitination at K254 (P = 0.0107);Loss of ubiquitination at K254 (P = 0.0107);
MVP		0.59
MPC		1.0
ClinPred		0.91	D
GERP RS		0.48
Varity_R		0.15
gMVP		0.77

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: rs115870061; hg19: chr3-43122162;