rs138980930

chr3-43080758-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2 BP4_Strong BP6_Very_Strong BS1

The NM_032806.6(POMGNT2):c.674G>A(p.Arg225Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000369 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. R225W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: POMGNT2 NM_032806.6 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.56

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 -14 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0106779635).
• BP6: Variant 3-43080758-C-T is Benign according to our data. Variant chr3-43080758-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262108.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 = 0.00188 (287/152296) while in subpopulation AFR AF= 0.00654 (272/41562). AF 95% confidence interval is 0.00591. There are 0 homozygotes in gnomad4. There are 130 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT2	NM_032806.6	c.674G>A	p.Arg225Gln	missense_variant	2/2	ENST00000344697.3
POMGNT2	XM_005265515.4	c.674G>A	p.Arg225Gln	missense_variant	3/3
POMGNT2	XM_011534163.3	c.674G>A	p.Arg225Gln	missense_variant	3/3
POMGNT2	XM_017007353.2	c.674G>A	p.Arg225Gln	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT2	ENST00000344697.3	c.674G>A	p.Arg225Gln	missense_variant	2/2	1	NM_032806.6	P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00654

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000538 AC: 135 AN: 250876 Hom.: 1 AF XY: 0.000368 AC XY: 50 AN XY: 135690

Gnomad AFR exome AF: 0.00608

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000211 AC: 308 AN: 1461782 Hom.: 0 Cov.: 37 AF XY: 0.000184 AC XY: 134 AN XY: 727192

Gnomad4 AFR exome AF: 0.00612

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.000506

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.000298

GnomAD4 genome AF: 0.00188 AC: 287 AN: 152296 Hom.: 0 Cov.: 33 AF XY: 0.00175 AC XY: 130 AN XY: 74482

Gnomad4 AFR AF: 0.00654

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000379 Hom.: 0

Bravo AF: 0.00219

ESP6500AA AF: 0.00635 AC: 28

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000708 AC: 86

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: 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

PreventionGenetics, part of Exact Sciences

-

- -

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.30
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.15
Sift	Benign	0.40	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.13	B;B
Vest4		0.35
MVP		0.70
MPC		0.62
ClinPred		0.016	T
GERP RS		4.8
Varity_R		0.10
gMVP		0.55

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: rs138980930; hg19: chr3-43122250;