rs2292486

chr1-46193238-G-Achr1-46193238-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017739.4(POMGNT1):c.1111-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,614,048 control chromosomes in the GnomAD database, including 5,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (473 hom., cov: 32)
  • Exomes 𝑓: 0.037 (5018 hom.)
• Consequence: POMGNT1 NM_017739.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.946

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]

TSPAN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-46193238-G-A is Benign according to our data. Variant chr1-46193238-G-A is described in ClinVar as [Benign]. Clinvar id is 260870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-46193238-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT1	NM_017739.4	c.1111-23C>T		intron_variant		ENST00000371984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT1	ENST00000371984.8	c.1111-23C>T		intron_variant		1	NM_017739.4	P1

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5658 AN: 152146 Hom.: 470 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0372

GnomAD3 exomes AF: 0.0673 AC: 16886 AN: 251078 Hom.: 1811 AF XY: 0.0720 AC XY: 9766 AN XY: 135716

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.0451

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.336

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.0175

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0485

GnomAD4 exome AF: 0.0375 AC: 54750 AN: 1461784 Hom.: 5018 Cov.: 33 AF XY: 0.0421 AC XY: 30645 AN XY: 727178

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.0418

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.0176

Gnomad4 NFE exome AF: 0.0144

Gnomad4 OTH exome AF: 0.0454

GnomAD4 genome AF: 0.0372 AC: 5663 AN: 152264 Hom.: 473 Cov.: 32 AF XY: 0.0428 AC XY: 3188 AN XY: 74432

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0199 Hom.: 24

Bravo AF: 0.0355

Asia WGS AF: 0.252 AC: 874 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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	-0.81
Cadd	Benign	13
Dann	Benign	0.62

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

Other links and lift over

dbSNP: rs2292486; hg19: chr1-46658910; COSMIC: COSV64341385; COSMIC: COSV64341385;