rs76693406

chr1-46196104-G-A

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.355-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,613,602 control chromosomes in the GnomAD database, including 811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (205 hom., cov: 33)
  • Exomes 𝑓: 0.022 (606 hom.)
• Consequence: POMGNT1 NM_017739.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.598

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=-0.86).
• BP6: Variant 1-46196104-G-A is Benign according to our data. Variant chr1-46196104-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-46196104-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT1	NM_017739.4	c.355-27C>T		intron_variant		ENST00000371984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT1	ENST00000371984.8	c.355-27C>T		intron_variant		1	NM_017739.4	P1

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6231 AN: 152142 Hom.: 205 Cov.: 33

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0291 AC: 7301 AN: 250734 Hom.: 181 AF XY: 0.0292 AC XY: 3956 AN XY: 135672

Gnomad AFR exome AF: 0.0883

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0280

Gnomad EAS exome AF: 0.000816

Gnomad SAS exome AF: 0.0434

Gnomad FIN exome AF: 0.0647

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0263

GnomAD4 exome AF: 0.0224 AC: 32806 AN: 1461342 Hom.: 606 Cov.: 31 AF XY: 0.0230 AC XY: 16745 AN XY: 726960

Gnomad4 AFR exome AF: 0.0950

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.0297

Gnomad4 EAS exome AF: 0.000554

Gnomad4 SAS exome AF: 0.0439

Gnomad4 FIN exome AF: 0.0611

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.0409 AC: 6235 AN: 152260 Hom.: 205 Cov.: 33 AF XY: 0.0422 AC XY: 3142 AN XY: 74454

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.0215

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0443

Gnomad4 FIN AF: 0.0669

Gnomad4 NFE AF: 0.0182

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0311 Hom.: 17

Bravo AF: 0.0393

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.4
Dann	Benign	0.61

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: rs76693406; hg19: chr1-46661776;