3-43080067-C-T

Position:

• chr3-43080067-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032806.6(POMGNT2):​c.1365G>A​(p.Pro455Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,613,634 control chromosomes in the GnomAD database, including 509,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48604 hom., cov: 33)
  • Exomes 𝑓: 0.79 (460706 hom.)
• Consequence: POMGNT2 NM_032806.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.20

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]

POMGNT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-43080067-C-T is Benign according to our data. Variant chr3-43080067-C-T is described in ClinVar as [Benign]. Clinvar id is 262104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-43080067-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMGNT2	NM_032806.6	c.1365G>A	p.Pro455Pro	synonymous_variant	2/2	ENST00000344697.3	NP_116195.2
POMGNT2	XM_005265515.4	c.1365G>A	p.Pro455Pro	synonymous_variant	3/3		XP_005265572.1
POMGNT2	XM_011534163.3	c.1365G>A	p.Pro455Pro	synonymous_variant	3/3		XP_011532465.1
POMGNT2	XM_017007353.2	c.1365G>A	p.Pro455Pro	synonymous_variant	4/4		XP_016862842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMGNT2	ENST00000344697.3	c.1365G>A	p.Pro455Pro	synonymous_variant	2/2	1	NM_032806.6	ENSP00000344125.2

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121502 AN: 152036 Hom.: 48566 Cov.: 33

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.795

GnomAD3 exomes AF: 0.789 AC: 197759 AN: 250752 Hom.: 78196 AF XY: 0.784 AC XY: 106320 AN XY: 135618

Gnomad AFR exome AF: 0.818

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.771

Gnomad EAS exome AF: 0.716

Gnomad SAS exome AF: 0.720

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.799

Gnomad OTH exome AF: 0.798

GnomAD4 exome AF: 0.793 AC: 1159142 AN: 1461480 Hom.: 460706 Cov.: 74 AF XY: 0.791 AC XY: 575097 AN XY: 727036

Gnomad4 AFR exome AF: 0.822

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.768

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.802

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.799 AC: 121597 AN: 152154 Hom.: 48604 Cov.: 33 AF XY: 0.799 AC XY: 59437 AN XY: 74378

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.795

Alfa AF: 0.795 Hom.: 85375

Bravo AF: 0.803

Asia WGS AF: 0.736 AC: 2560 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.23
DANN	Benign	0.76

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: rs604033; hg19: chr3-43121559; COSMIC: COSV60955172;