rs147429438

Variant names:

• chr3-43080871-G-A
• rs147429438
• NM_032806.6:c.561C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-43080871-G-A
• chr3-43080871-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS1

The NM_032806.6(POMGNT2):​c.561C>T​(p.His187His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,613,998 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00062 (1 hom.)
• Consequence: POMGNT2 NM_032806.6 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:4
• Conservation: PhyloP100: -1.25
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-43080871-G-A is Benign according to our data. Variant chr3-43080871-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 262107.
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000565 (86/152190) while in subpopulation AMR AF = 0.00294 (45/15286). AF 95% confidence interval is 0.00226. There are 0 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.561C>T	p.His187His	synonymous	Exon 2 of 2	NP_116195.2
	POMGNT2	NM_001437285.1		c.561C>T	p.His187His	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.561C>T	p.His187His	synonymous	Exon 2 of 2	ENSP00000344125.2	Q8NAT1
	POMGNT2	ENST00000441964.1	TSL:4	c.561C>T	p.His187His	synonymous	Exon 3 of 3	ENSP00000408992.1	Q8NAT1
	POMGNT2	ENST00000686643.1		c.561C>T	p.His187His	synonymous	Exon 4 of 4	ENSP00000509123.1	Q8NAT1

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

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: 0.000441

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000390 AC: 98 AN: 251094 AF XY: 0.000368

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000520

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000623 AC: 911 AN: 1461808 Hom.: 1 Cov.: 37 AF XY: 0.000583 AC XY: 424 AN XY: 727210

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00123 AC: 55 AN: 44722

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000724 AC: 805 AN: 1111982

Other (OTH) AF: 0.000712 AC: 43 AN: 60392

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.000619 AC XY: 46 AN XY: 74336

African (AFR) AF: 0.000145 AC: 6 AN: 41454

American (AMR) AF: 0.00294 AC: 45 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68032

Other (OTH) AF: 0.00239 AC: 5 AN: 2090

Alfa AF: 0.000229 Hom.: 0

Bravo AF: 0.000937

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	2	not specified (3)
-	-	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	-0.83
CADD	Benign	0.45
DANN	Benign	0.56
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs147429438; hg19: chr3-43122363; COSMIC: COSV60953740;