rs147175064

Positions:

• chr3-43080048-G-A

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.1384C>T​(p.Arg462Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00131 in 1,613,824 control chromosomes in the GnomAD database, including 25 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. R462L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0071 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00071 (11 hom.)
• Consequence: POMGNT2 NM_032806.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.59

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=0.00639081).
• BP6: Variant 3-43080048-G-A is Benign according to our data. Variant chr3-43080048-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 386897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-43080048-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00706 (1076/152342) while in subpopulation AFR AF= 0.0242 (1006/41588). AF 95% confidence interval is 0.0229. There are 14 homozygotes in gnomad4. There are 525 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT2	NM_032806.6	c.1384C>T	p.Arg462Trp	missense_variant	2/2	ENST00000344697.3
POMGNT2	XM_005265515.4	c.1384C>T	p.Arg462Trp	missense_variant	3/3
POMGNT2	XM_011534163.3	c.1384C>T	p.Arg462Trp	missense_variant	3/3
POMGNT2	XM_017007353.2	c.1384C>T	p.Arg462Trp	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT2	ENST00000344697.3	c.1384C>T	p.Arg462Trp	missense_variant	2/2	1	NM_032806.6	P1

Frequencies

GnomAD3 genomes AF: 0.00706 AC: 1074 AN: 152224 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00172 AC: 432 AN: 250790 Hom.: 3 AF XY: 0.00141 AC XY: 191 AN XY: 135624

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.000708 AC: 1035 AN: 1461482 Hom.: 11 Cov.: 29 AF XY: 0.000615 AC XY: 447 AN XY: 727050

Gnomad4 AFR exome AF: 0.0250

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000270

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00706 AC: 1076 AN: 152342 Hom.: 14 Cov.: 33 AF XY: 0.00705 AC XY: 525 AN XY: 74492

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00137 Hom.: 2

Bravo AF: 0.00814

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0234 AC: 103

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00220 AC: 267

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 07, 2017

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.95	D
MetaRNN	Benign	0.0064	T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.63
MVP		0.78
MPC		0.70
ClinPred		0.029	T
GERP RS		4.6
Varity_R		0.15
gMVP		0.79

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: rs147175064; hg19: chr3-43121540;