rs375314883

chr3-43080994-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_032806.6(POMGNT2):c.438G>A(p.Pro146=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000681 in 1,614,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000042 (1 hom.)
• Consequence: POMGNT2 NM_032806.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -8.52

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 -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 3-43080994-C-T is Benign according to our data. Variant chr3-43080994-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 385702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.52 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000322 (49/152320) while in subpopulation AFR AF= 0.000842 (35/41582). AF 95% confidence interval is 0.000621. There are 0 homozygotes in gnomad4. There are 27 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.438G>A	p.Pro146=	synonymous_variant	2/2	ENST00000344697.3
POMGNT2	XM_005265515.4	c.438G>A	p.Pro146=	synonymous_variant	3/3
POMGNT2	XM_011534163.3	c.438G>A	p.Pro146=	synonymous_variant	3/3
POMGNT2	XM_017007353.2	c.438G>A	p.Pro146=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT2	ENST00000344697.3	c.438G>A	p.Pro146=	synonymous_variant	2/2	1	NM_032806.6	P1

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000716 AC: 18 AN: 251418 Hom.: 0 AF XY: 0.0000589 AC XY: 8 AN XY: 135882

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.0000289

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000417 AC: 61 AN: 1461878 Hom.: 1 Cov.: 37 AF XY: 0.0000426 AC XY: 31 AN XY: 727238

Gnomad4 AFR exome AF: 0.000866

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74478

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000195 Hom.: 0

Bravo AF: 0.000453

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

GeneDx

Apr 25, 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. -

POMGNT2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.079
Dann	Benign	0.61

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: rs375314883; hg19: chr3-43122486;