Variant rs78405727 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.1785+31C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 1,612,978 control chromosomes in the GnomAD database, including 1,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 359 hom., cov: 32)

Exomes 𝑓: 0.023 ( 717 hom. )

Consequence

POMGNT1
NM_017739.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.86

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:

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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=-0.89).

BP6

Variant 1-46189823-G-T is Benign according to our data. Variant chr1-46189823-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 260871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-46189823-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 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.1785+31C>A		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.1785+31C>A		intron_variant		1	NM_017739.4	ENSP00000361052.3		Q8WZA1-1

Frequencies

GnomAD3 genomes

AF:

0.0503

AC:

7655

AN:

152176

Hom.:

358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0260

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.0668

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0311

AC:

7712

AN:

248058

Hom.:

229

AF XY:

0.0302

AC XY:

4043

AN XY:

133766

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.000821

Gnomad SAS exome

AF:

0.0385

Gnomad FIN exome

AF:

0.0646

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0285

GnomAD4 exome

AF:

0.0232

AC:

33927

AN:

1460684

Hom.:

717

Cov.:

AF XY:

0.0235

AC XY:

17061

AN XY:

726502

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0298

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.0397

Gnomad4 FIN exome

AF:

0.0611

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0292

GnomAD4 genome

AF:

0.0504

AC:

7677

AN:

152294

Hom.:

359

Cov.:

AF XY:

0.0515

AC XY:

3837

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.0259

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0400

Gnomad4 FIN

AF:

0.0668

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0301

Hom.:

Bravo

AF:

0.0501

Asia WGS

AF:

0.0330

AC:

115

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

-0.89

CADD

Benign

0.045

DANN

Benign

0.72

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