rs34083889

chr3-43080047-C-Achr3-43080047-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032806.6(POMGNT2):c.1385G>T(p.Arg462Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,613,812 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R462Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.013 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (31 hom.)
• Consequence: POMGNT2 NM_032806.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.74

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004484147).
• BP6: Variant 3-43080047-C-A is Benign according to our data. Variant chr3-43080047-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 377356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1930/152304) while in subpopulation AFR AF= 0.0438 (1821/41550). AF 95% confidence interval is 0.0422. There are 33 homozygotes in gnomad4. There are 912 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT2	NM_032806.6	c.1385G>T	p.Arg462Leu	missense_variant	2/2	ENST00000344697.3
POMGNT2	XM_005265515.4	c.1385G>T	p.Arg462Leu	missense_variant	3/3
POMGNT2	XM_011534163.3	c.1385G>T	p.Arg462Leu	missense_variant	3/3
POMGNT2	XM_017007353.2	c.1385G>T	p.Arg462Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT2	ENST00000344697.3	c.1385G>T	p.Arg462Leu	missense_variant	2/2	1	NM_032806.6	P1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1930 AN: 152188 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00337 AC: 846 AN: 250758 Hom.: 12 AF XY: 0.00258 AC XY: 350 AN XY: 135606

Gnomad AFR exome AF: 0.0437

Gnomad AMR exome AF: 0.00330

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: 0.0000883

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00127 AC: 1854 AN: 1461508 Hom.: 31 Cov.: 29 AF XY: 0.00109 AC XY: 792 AN XY: 727076

Gnomad4 AFR exome AF: 0.0441

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000378

Gnomad4 OTH exome AF: 0.00252

GnomAD4 genome AF: 0.0127 AC: 1930 AN: 152304 Hom.: 33 Cov.: 33 AF XY: 0.0122 AC XY: 912 AN XY: 74468

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.00509

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00127 Hom.: 3

Bravo AF: 0.0147

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0422 AC: 186

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00429 AC: 521

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 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. -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jan 13, 2017

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8;C4748320:Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.074	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.0045	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.046	D;D
Polyphen		0.65	P;P
Vest4		0.62
MVP		0.82
MPC		0.42
ClinPred		0.013	T
GERP RS		5.5
Varity_R		0.20
gMVP		0.78

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: rs34083889; hg19: chr3-43121539;