Variant 1-46196937-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:4

Conservation

PhyloP100: 0.318

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 260873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-46196937-A-C is described in Lovd as [Benign].

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/exons	MANE	UniProt
POMGNT1	NM_017739.4 linkuse as main transcript	c.235+33T>G		intron_variant		ENST00000371984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT1	ENST00000371984.8 linkuse as main transcript	c.235+33T>G		intron_variant		1	NM_017739.4	P1	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

GnomAD3 exomes

AF:

0.0291

AC:

7319

AN:

251488

Hom.:

181

AF XY:

0.0292

AC XY:

3965

AN XY:

135918

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 SAS exome

AF:

0.0434

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

Gnomad4 AFR exome

AF:

0.0950

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0297

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.0440

Gnomad4 FIN exome

AF:

0.0611

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0409

AC:

6232

AN:

152226

Hom.:

203

Cov.:

AF XY:

0.0422

AC XY:

3143

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0855

Gnomad4 AMR

AF:

0.0213

Gnomad4 ASJ

AF:

0.0309

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0444

Gnomad4 FIN

AF:

0.0672

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0298

Hom.:

Bravo

AF:

0.0393

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Retinitis pigmentosa 76

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over