NM_017739.4:c.1895+30A>G

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.1895+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,613,462 control chromosomes in the GnomAD database, including 1,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 407 hom., cov: 32)

Exomes 𝑓: 0.025 ( 870 hom. )

Consequence

POMGNT1
NM_017739.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.589

Publications

5 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 links:

TSPAN1 (HGNC:20657): (tetraspanin 1) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]

TSPAN1 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=-0.92).

BP6

Variant 1-46189428-T-C is Benign according to our data. Variant chr1-46189428-T-C is described in ClinVar as Benign. ClinVar VariationId is 257665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMGNT1	NM_017739.4 link	c.1895+30A>G		intron_variant	Intron 21 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.1895+30A>G		intron_variant	Intron 21 of 21	1	NM_017739.4	ENSP00000361052.3		Q8WZA1-1

Frequencies

GnomAD3 genomes

AF:

0.0537

AC:

8172

AN:

152124

Hom.:

405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0264

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.0628

Gnomad FIN

AF:

0.0668

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0185

Gnomad OTH

AF:

0.0436

GnomAD2 exomes

AF:

0.0352

AC:

8769

AN:

249182

AF XY:

0.0350

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0281

Gnomad EAS exome

AF:

0.0151

Gnomad FIN exome

AF:

0.0647

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0298

GnomAD4 exome

AF:

0.0251

AC:

36608

AN:

1461220

Hom.:

870

Cov.:

AF XY:

0.0258

AC XY:

18762

AN XY:

726804

show subpopulations

African (AFR)

AF:

0.138

AC:

4630

AN:

33466

American (AMR)

AF:

0.0156

AC:

695

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.0298

AC:

777

AN:

26108

East Asian (EAS)

AF:

0.0134

AC:

530

AN:

39694

South Asian (SAS)

AF:

0.0590

AC:

5083

AN:

86148

European-Finnish (FIN)

AF:

0.0611

AC:

3259

AN:

53380

Middle Eastern (MID)

AF:

0.0302

AC:

174

AN:

5760

European-Non Finnish (NFE)

AF:

0.0176

AC:

19519

AN:

1111660

Other (OTH)

AF:

0.0322

AC:

1941

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

2228

4457

6685

8914

11142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.0539

AC:

8202

AN:

152242

Hom.:

407

Cov.:

AF XY:

0.0552

AC XY:

4108

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.126

AC:

5238

AN:

41538

American (AMR)

AF:

0.0263

AC:

402

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

108

AN:

3470

East Asian (EAS)

AF:

0.0153

AC:

AN:

5174

South Asian (SAS)

AF:

0.0630

AC:

304

AN:

4822

European-Finnish (FIN)

AF:

0.0668

AC:

708

AN:

10602

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0185

AC:

1258

AN:

68012

Other (OTH)

AF:

0.0431

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

388

776

1164

1552

1940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0348

Hom.:

Bravo

AF:

0.0535

Asia WGS

AF:

0.0500

AC:

172

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

Jun 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.92

CADD

Benign

3.0

(source)

DANN

Benign

0.65

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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