rs7527668

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017739.4(POMGNT1):c.1027-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,602,566 control chromosomes in the GnomAD database, including 105,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11099 hom., cov: 33)

Exomes 𝑓: 0.36 ( 94621 hom. )

Consequence

POMGNT1
NM_017739.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.303

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:

POMGNT1 (HGNC:):

POMGNT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-46193432-T-C is Benign according to our data. Variant chr1-46193432-T-C is described in ClinVar as [Benign]. Clinvar id is 260869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-46193432-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMGNT1	NM_017739.4 linkuse as main transcript	c.1027-44A>G		intron_variant		ENST00000371984.8	NP_060209.4	Q8WZA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMGNT1	ENST00000371984.8 linkuse as main transcript	c.1027-44A>G		intron_variant		1	NM_017739.4	ENSP00000361052.3		Q8WZA1-1

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57311

AN:

151934

Hom.:

11081

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.363

GnomAD3 exomes

AF:

0.365

AC:

84019

AN:

230100

Hom.:

15747

AF XY:

0.367

AC XY:

45476

AN XY:

124054

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.393

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.358

AC:

518812

AN:

1450514

Hom.:

94621

Cov.:

AF XY:

0.360

AC XY:

259664

AN XY:

720432

show subpopulations

Gnomad4 AFR exome

AF:

0.459

Gnomad4 AMR exome

AF:

0.393

Gnomad4 ASJ exome

AF:

0.326

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.449

Gnomad4 FIN exome

AF:

0.395

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.350

GnomAD4 genome

AF:

0.377

AC:

57398

AN:

152052

Hom.:

11099

Cov.:

AF XY:

0.379

AC XY:

28168

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.446

Gnomad4 AMR

AF:

0.373

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.384

Gnomad4 NFE

AF:

0.353

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.354

Hom.:

10241

Bravo

AF:

0.375

Asia WGS

AF:

0.294

AC:

1025

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive limb-girdle muscular dystrophy type 2O

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Retinitis pigmentosa 76

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

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

-0.89

CADD

Benign

6.6

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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