chr1-46196104-G-A

Variant names:

• chr1-46196104-G-A
• rs76693406
• NM_017739.4:c.355-27C>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.598
• Publications: 3 publications found

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: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]

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 260874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017739.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	NM_017739.4	MANE Select	c.355-27C>T		intron	N/A	NP_060209.4
	POMGNT1	NM_001243766.2		c.355-27C>T		intron	N/A	NP_001230695.2
	POMGNT1	NM_001410783.1		c.355-27C>T		intron	N/A	NP_001397712.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	ENST00000371984.8	TSL:1 MANE Select	c.355-27C>T		intron	N/A	ENSP00000361052.3
	POMGNT1	ENST00000685775.1		n.1273C>T		non_coding_transcript_exon	Exon 3 of 12
	POMGNT1	ENST00000686252.1		n.1402C>T		non_coding_transcript_exon	Exon 3 of 20

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

GnomAD2 exomes AF: 0.0291 AC: 7301 AN: 250734 AF XY: 0.0292

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 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

African (AFR) AF: 0.0950 AC: 3179 AN: 33466

American (AMR) AF: 0.0135 AC: 605 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 777 AN: 26134

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39698

South Asian (SAS) AF: 0.0439 AC: 3788 AN: 86216

European-Finnish (FIN) AF: 0.0611 AC: 3249 AN: 53176

Middle Eastern (MID) AF: 0.0265 AC: 148 AN: 5588

European-Non Finnish (NFE) AF: 0.0175 AC: 19447 AN: 1111990

Other (OTH) AF: 0.0264 AC: 1591 AN: 60356

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

African (AFR) AF: 0.0855 AC: 3550 AN: 41534

American (AMR) AF: 0.0215 AC: 329 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4830

European-Finnish (FIN) AF: 0.0669 AC: 709 AN: 10598

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0182 AC: 1238 AN: 68020

Other (OTH) AF: 0.0327 AC: 69 AN: 2110

Alfa AF: 0.0439 Hom.: 97

Bravo AF: 0.0393

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs76693406; hg19: chr1-46661776;