chr3-43079944-G-A

Position:

• chr3-43079944-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032806.6(POMGNT2):​c.1488C>T​(p.Gly496Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,613,972 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (11 hom., cov: 33)
  • Exomes 𝑓: 0.015 (197 hom.)
• Consequence: POMGNT2 NM_032806.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.789

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=-0.83).
• BP6: Variant 3-43079944-G-A is Benign according to our data. Variant chr3-43079944-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-43079944-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.789 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00965 (1470/152334) while in subpopulation NFE AF= 0.0156 (1063/68030). AF 95% confidence interval is 0.0148. There are 11 homozygotes in gnomad4. There are 681 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMGNT2	NM_032806.6	c.1488C>T	p.Gly496Gly	synonymous_variant	2/2	ENST00000344697.3	NP_116195.2
POMGNT2	XM_005265515.4	c.1488C>T	p.Gly496Gly	synonymous_variant	3/3		XP_005265572.1
POMGNT2	XM_011534163.3	c.1488C>T	p.Gly496Gly	synonymous_variant	3/3		XP_011532465.1
POMGNT2	XM_017007353.2	c.1488C>T	p.Gly496Gly	synonymous_variant	4/4		XP_016862842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMGNT2	ENST00000344697.3	c.1488C>T	p.Gly496Gly	synonymous_variant	2/2	1	NM_032806.6	ENSP00000344125.2

Frequencies

GnomAD3 genomes AF: 0.00966 AC: 1470 AN: 152216 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.0103 AC: 2573 AN: 250656 Hom.: 19 AF XY: 0.0102 AC XY: 1383 AN XY: 135556

Gnomad AFR exome AF: 0.00241

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00828

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.0144

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.00850

GnomAD4 exome AF: 0.0148 AC: 21681 AN: 1461638 Hom.: 197 Cov.: 29 AF XY: 0.0144 AC XY: 10451 AN XY: 727134

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.00769

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00158

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.00984

GnomAD4 genome AF: 0.00965 AC: 1470 AN: 152334 Hom.: 11 Cov.: 33 AF XY: 0.00914 AC XY: 681 AN XY: 74494

Gnomad4 AFR AF: 0.00269

Gnomad4 AMR AF: 0.00398

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.0134 Hom.: 11

Bravo AF: 0.00886

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0129

EpiControl AF: 0.0157

ClinVar

Significance: Benign/Likely 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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 19, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.19
DANN	Benign	0.63

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: rs35207939; hg19: chr3-43121436; COSMIC: COSV60954990;