rs113174528

chr1-46189428-T-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.1895+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,613,462 control chromosomes in the GnomAD database, including 1,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (407 hom., cov: 32)
  • Exomes 𝑓: 0.025 (870 hom.)
• Consequence: POMGNT1 NM_017739.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.589

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=-0.92).
• BP6: Variant 1-46189428-T-C is Benign according to our data. Variant chr1-46189428-T-C is described in ClinVar as [Benign]. Clinvar id is 257665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-46189428-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT1	NM_017739.4	c.1895+30A>G		intron_variant		ENST00000371984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT1	ENST00000371984.8	c.1895+30A>G		intron_variant		1	NM_017739.4	P1

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8172 AN: 152124 Hom.: 405 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0436

GnomAD3 exomes AF: 0.0352 AC: 8769 AN: 249182 Hom.: 279 AF XY: 0.0350 AC XY: 4722 AN XY: 134770

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.0281

Gnomad EAS exome AF: 0.0151

Gnomad SAS exome AF: 0.0586

Gnomad FIN exome AF: 0.0647

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0298

GnomAD4 exome AF: 0.0251 AC: 36608 AN: 1461220 Hom.: 870 Cov.: 30 AF XY: 0.0258 AC XY: 18762 AN XY: 726804

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0298

Gnomad4 EAS exome AF: 0.0134

Gnomad4 SAS exome AF: 0.0590

Gnomad4 FIN exome AF: 0.0611

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0322

GnomAD4 genome AF: 0.0539 AC: 8202 AN: 152242 Hom.: 407 Cov.: 32 AF XY: 0.0552 AC XY: 4108 AN XY: 74428

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0363 Hom.: 53

Bravo AF: 0.0535

Asia WGS AF: 0.0500 AC: 172 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	-0.92
Cadd	Benign	3.0
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs113174528; hg19: chr1-46655100;