chr1-46196937-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017739.4(POMGNT1):c.235+33T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,614,094 control chromosomes in the GnomAD database, including 808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 203 hom., cov: 33)

Exomes 𝑓: 0.022 ( 605 hom. )

Consequence

POMGNT1
NM_017739.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.318

Publications

4 publications found

Variant links:

Genes affected

POMGNT1 (HGNC:19139): (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)) This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

POMGNT1 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy type 2O
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3
Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: G2P, Ambry Genetics
myopathy caused by variation in POMGNT1
Inheritance: AR Classification: STRONG Submitted by: ClinGen
retinitis pigmentosa 76
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with cerebellar involvement
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POMGNT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-46196937-A-C is Benign according to our data. Variant chr1-46196937-A-C is described in ClinVar as Benign. ClinVar VariationId is 260873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMGNT1	NM_017739.4 link	c.235+33T>G		intron_variant	Intron 3 of 21	ENST00000371984.8	NP_060209.4	Q8WZA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT1	ENST00000371984.8 link	c.235+33T>G		intron_variant	Intron 3 of 21	1	NM_017739.4	ENSP00000361052.3		Q8WZA1-1

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6228

AN:

152108

Hom.:

203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0856

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.0309

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0441

Gnomad FIN

AF:

0.0672

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0335

GnomAD2 exomes

AF:

0.0291

AC:

7319

AN:

251488

AF XY:

0.0292

show subpopulations

Gnomad AFR exome

AF:

0.0882

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0281

Gnomad EAS exome

AF:

0.000815

Gnomad FIN exome

AF:

0.0646

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0225

AC:

32831

AN:

1461868

Hom.:

605

Cov.:

AF XY:

0.0231

AC XY:

16763

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0950

AC:

3182

AN:

33480

American (AMR)

AF:

0.0135

AC:

605

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

777

AN:

26136

East Asian (EAS)

AF:

0.000554

AC:

AN:

39700

South Asian (SAS)

AF:

0.0440

AC:

3792

AN:

86256

European-Finnish (FIN)

AF:

0.0611

AC:

3261

AN:

53408

Middle Eastern (MID)

AF:

0.0264

AC:

152

AN:

5768

European-Non Finnish (NFE)

AF:

0.0175

AC:

19446

AN:

1112002

Other (OTH)

AF:

0.0264

AC:

1594

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

2577

5154

7730

10307

12884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

812

1624

2436

3248

4060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0409

AC:

6232

AN:

152226

Hom.:

203

Cov.:

AF XY:

0.0422

AC XY:

3143

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0855

AC:

3549

AN:

41526

American (AMR)

AF:

0.0213

AC:

325

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0309

AC:

107

AN:

3466

East Asian (EAS)

AF:

0.00135

AC:

AN:

5180

South Asian (SAS)

AF:

0.0444

AC:

214

AN:

4822

European-Finnish (FIN)

AF:

0.0672

AC:

713

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0182

AC:

1236

AN:

68004

Other (OTH)

AF:

0.0331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

304

608

912

1216

1520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0314

Hom.:

Bravo

AF:

0.0393

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 76

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.43

PhyloP100

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over