chr3-43080067-C-T

Variant names:

• chr3-43080067-C-T
• rs604033
• NM_032806.6:c.1365G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032806.6(POMGNT2):​c.1365G>A​(p.Pro455Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,613,634 control chromosomes in the GnomAD database, including 509,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P455P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.80 (48604 hom., cov: 33)
  • Exomes 𝑓: 0.79 (460706 hom.)
• Consequence: POMGNT2 NM_032806.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.20
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• myopathy caused by variation in POMGNT2

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-43080067-C-T is Benign according to our data. Variant chr3-43080067-C-T is described in ClinVar as Benign. ClinVar VariationId is 262104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032806.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT2	NM_032806.6	MANE Select	c.1365G>A	p.Pro455Pro	synonymous	Exon 2 of 2	NP_116195.2
	POMGNT2	NM_001437285.1		c.1365G>A	p.Pro455Pro	synonymous	Exon 3 of 3	NP_001424214.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT2	ENST00000344697.3	TSL:1 MANE Select	c.1365G>A	p.Pro455Pro	synonymous	Exon 2 of 2	ENSP00000344125.2
	POMGNT2	ENST00000441964.1	TSL:4	c.1365G>A	p.Pro455Pro	synonymous	Exon 3 of 3	ENSP00000408992.1
	POMGNT2	ENST00000686643.1		c.1365G>A	p.Pro455Pro	synonymous	Exon 4 of 4	ENSP00000509123.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121502 AN: 152036 Hom.: 48566 Cov.: 33

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.795

GnomAD2 exomes AF: 0.789 AC: 197759 AN: 250752 AF XY: 0.784

Gnomad AFR exome AF: 0.818

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.771

Gnomad EAS exome AF: 0.716

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.799

Gnomad OTH exome AF: 0.798

GnomAD4 exome AF: 0.793 AC: 1159142 AN: 1461480 Hom.: 460706 Cov.: 74 AF XY: 0.791 AC XY: 575097 AN XY: 727036

African (AFR) AF: 0.822 AC: 27530 AN: 33480

American (AMR) AF: 0.825 AC: 36910 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 20074 AN: 26134

East Asian (EAS) AF: 0.707 AC: 28075 AN: 39694

South Asian (SAS) AF: 0.720 AC: 62119 AN: 86246

European-Finnish (FIN) AF: 0.802 AC: 42598 AN: 53126

Middle Eastern (MID) AF: 0.794 AC: 4578 AN: 5766

European-Non Finnish (NFE) AF: 0.800 AC: 889955 AN: 1111930

Other (OTH) AF: 0.783 AC: 47303 AN: 60388

GnomAD4 genome AF: 0.799 AC: 121597 AN: 152154 Hom.: 48604 Cov.: 33 AF XY: 0.799 AC XY: 59437 AN XY: 74378

African (AFR) AF: 0.817 AC: 33926 AN: 41524

American (AMR) AF: 0.803 AC: 12273 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2660 AN: 3472

East Asian (EAS) AF: 0.718 AC: 3692 AN: 5144

South Asian (SAS) AF: 0.730 AC: 3514 AN: 4816

European-Finnish (FIN) AF: 0.819 AC: 8694 AN: 10612

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54184 AN: 67980

Other (OTH) AF: 0.795 AC: 1678 AN: 2112

Alfa AF: 0.795 Hom.: 187544

Bravo AF: 0.803

Asia WGS AF: 0.736 AC: 2560 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (2)
-	-	2	not specified (2)
-	-	1	Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.23
DANN	Benign	0.76
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs604033; hg19: chr3-43121559; COSMIC: COSV60955172;