Variant rs115804669 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017739.4(POMGNT1):c.880-39G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,610,962 control chromosomes in the GnomAD database, including 545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 76 hom., cov: 33)

Exomes 𝑓: 0.021 ( 469 hom. )

Consequence

POMGNT1
NM_017739.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.912

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=-0.84).

BP6

Variant 1-46193964-C-G is Benign according to our data. Variant chr1-46193964-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-46193964-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0281 (4279/152278) while in subpopulation SAS AF= 0.0433 (209/4822). AF 95% confidence interval is 0.0392. There are 76 homozygotes in gnomad4. There are 2278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMGNT1	NM_017739.4 linkuse as main transcript	c.880-39G>C		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.880-39G>C		intron_variant		1	NM_017739.4	ENSP00000361052.3		Q8WZA1-1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4273

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0431

Gnomad FIN

AF:

0.0670

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0258

AC:

6330

AN:

245278

Hom.:

124

AF XY:

0.0268

AC XY:

3554

AN XY:

132410

show subpopulations

Gnomad AFR exome

AF:

0.0435

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0282

Gnomad EAS exome

AF:

0.000830

Gnomad SAS exome

AF:

0.0437

Gnomad FIN exome

AF:

0.0646

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0247

GnomAD4 exome

AF:

0.0210

AC:

30592

AN:

1458684

Hom.:

469

Cov.:

AF XY:

0.0217

AC XY:

15764

AN XY:

725246

show subpopulations

Gnomad4 AFR exome

AF:

0.0442

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.0297

Gnomad4 EAS exome

AF:

0.000555

Gnomad4 SAS exome

AF:

0.0439

Gnomad4 FIN exome

AF:

0.0609

Gnomad4 NFE exome

AF:

0.0174

Gnomad4 OTH exome

AF:

0.0228

GnomAD4 genome

AF:

0.0281

AC:

4279

AN:

152278

Hom.:

Cov.:

AF XY:

0.0306

AC XY:

2278

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0433

Gnomad4 FIN

AF:

0.0670

Gnomad4 NFE

AF:

0.0180

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0242

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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 28, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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