rs149932476

Variant names:

• chr3-43080895-C-G
• rs149932476
• NM_032806.6:c.537G>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_032806.6(POMGNT2):​c.537G>C​(p.Leu179Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000952 in 1,614,160 control chromosomes in the GnomAD database, including 10 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. L179L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0041 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00062 (9 hom.)
• Consequence: POMGNT2 NM_032806.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.81
• Publications: 0 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 3-43080895-C-G is Benign according to our data. Variant chr3-43080895-C-G is described in ClinVar as Benign. ClinVar VariationId is 382900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.81 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0041 (624/152300) while in subpopulation AFR AF = 0.0135 (562/41574). AF 95% confidence interval is 0.0126. There are 1 homozygotes in GnomAd4. There are 297 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.537G>C	p.Leu179Leu	synonymous	Exon 2 of 2	NP_116195.2
	POMGNT2	NM_001437285.1		c.537G>C	p.Leu179Leu	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.537G>C	p.Leu179Leu	synonymous	Exon 2 of 2	ENSP00000344125.2	Q8NAT1
	POMGNT2	ENST00000441964.1	TSL:4	c.537G>C	p.Leu179Leu	synonymous	Exon 3 of 3	ENSP00000408992.1	Q8NAT1
	POMGNT2	ENST00000686643.1		c.537G>C	p.Leu179Leu	synonymous	Exon 4 of 4	ENSP00000509123.1	Q8NAT1

Frequencies

GnomAD3 genomes AF: 0.00411 AC: 625 AN: 152182 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00119 AC: 299 AN: 251244 AF XY: 0.000795

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.000624 AC: 912 AN: 1461860 Hom.: 9 Cov.: 37 AF XY: 0.000561 AC XY: 408 AN XY: 727232

African (AFR) AF: 0.0162 AC: 544 AN: 33480

American (AMR) AF: 0.00215 AC: 96 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.000108 AC: 120 AN: 1111998

Other (OTH) AF: 0.00169 AC: 102 AN: 60396

GnomAD4 genome AF: 0.00410 AC: 624 AN: 152300 Hom.: 1 Cov.: 33 AF XY: 0.00399 AC XY: 297 AN XY: 74464

African (AFR) AF: 0.0135 AC: 562 AN: 41574

American (AMR) AF: 0.00275 AC: 42 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00134 Hom.: 1

Bravo AF: 0.00478

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.4
DANN	Benign	0.67
PhyloP100		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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: rs149932476; hg19: chr3-43122387;