rs9811883

Variant names:

• chr3-43080199-C-T
• rs9811883
• NM_032806.6:c.1233G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-43080199-C-T
• chr3-43080199-C-G

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.1233G>A​(p.Gln411Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 1,613,968 control chromosomes in the GnomAD database, including 1,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (474 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (530 hom.)
• Consequence: POMGNT2 NM_032806.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.654
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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=-0.48).
• BP6: Variant 3-43080199-C-T is Benign according to our data. Variant chr3-43080199-C-T is described in ClinVar as Benign. ClinVar VariationId is 262103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.654 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 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.1233G>A	p.Gln411Gln	synonymous	Exon 2 of 2	NP_116195.2
	POMGNT2	NM_001437285.1		c.1233G>A	p.Gln411Gln	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.1233G>A	p.Gln411Gln	synonymous	Exon 2 of 2	ENSP00000344125.2	Q8NAT1
	POMGNT2	ENST00000441964.1	TSL:4	c.1233G>A	p.Gln411Gln	synonymous	Exon 3 of 3	ENSP00000408992.1	Q8NAT1
	POMGNT2	ENST00000686643.1		c.1233G>A	p.Gln411Gln	synonymous	Exon 4 of 4	ENSP00000509123.1	Q8NAT1

Frequencies

GnomAD3 genomes AF: 0.0441 AC: 6715 AN: 152152 Hom.: 473 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.0397

GnomAD2 exomes AF: 0.0131 AC: 3289 AN: 250870 AF XY: 0.00981

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.0132

Gnomad ASJ exome AF: 0.00418

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00149

Gnomad OTH exome AF: 0.0140

GnomAD4 exome AF: 0.00561 AC: 8195 AN: 1461698 Hom.: 530 Cov.: 37 AF XY: 0.00500 AC XY: 3637 AN XY: 727154

African (AFR) AF: 0.161 AC: 5385 AN: 33478

American (AMR) AF: 0.0139 AC: 622 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00421 AC: 110 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000591 AC: 51 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53340

Middle Eastern (MID) AF: 0.0283 AC: 163 AN: 5766

European-Non Finnish (NFE) AF: 0.000934 AC: 1039 AN: 1111918

Other (OTH) AF: 0.0136 AC: 824 AN: 60388

GnomAD4 genome AF: 0.0442 AC: 6734 AN: 152270 Hom.: 474 Cov.: 33 AF XY: 0.0433 AC XY: 3224 AN XY: 74462

African (AFR) AF: 0.148 AC: 6155 AN: 41516

American (AMR) AF: 0.0219 AC: 335 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00147 AC: 100 AN: 68022

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0182 Hom.: 454

Bravo AF: 0.0509

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.00218

EpiControl AF: 0.00207

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.0
DANN	Benign	0.63
PhyloP100		0.65
Mutation Taster		=97/3	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: rs9811883; hg19: chr3-43121691; COSMIC: COSV60954294;