rs78405727

Variant names:

• chr1-46189823-G-T
• rs78405727
• NM_017739.4:c.1785+31C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001243766.2(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_001243766.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.86
• Publications: 4 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=-0.89).
• BP6: Variant 1-46189823-G-T is Benign according to our data. Variant chr1-46189823-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243766.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	NM_017739.4	MANE Select	c.1785+31C>A		intron	N/A	NP_060209.4
	POMGNT1	NM_001243766.2		c.1785+31C>A		intron	N/A	NP_001230695.2
	POMGNT1	NM_001410783.1		c.1785+31C>A		intron	N/A	NP_001397712.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	ENST00000371984.8	TSL:1 MANE Select	c.1785+31C>A		intron	N/A	ENSP00000361052.3
	POMGNT1	ENST00000371992.1	TSL:2	c.1785+31C>A		intron	N/A	ENSP00000361060.1
	POMGNT1	ENST00000692369.1		c.1785+31C>A		intron	N/A	ENSP00000508453.1

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 7655 AN: 152176 Hom.: 358 Cov.: 32

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

GnomAD2 exomes AF: 0.0311 AC: 7712 AN: 248058 AF XY: 0.0302

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 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.: 33 AF XY: 0.0235 AC XY: 17061 AN XY: 726502

African (AFR) AF: 0.130 AC: 4348 AN: 33472

American (AMR) AF: 0.0154 AC: 690 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0298 AC: 774 AN: 25946

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39692

South Asian (SAS) AF: 0.0397 AC: 3411 AN: 85818

European-Finnish (FIN) AF: 0.0611 AC: 3260 AN: 53394

Middle Eastern (MID) AF: 0.0290 AC: 161 AN: 5550

European-Non Finnish (NFE) AF: 0.0175 AC: 19498 AN: 1111804

Other (OTH) AF: 0.0292 AC: 1763 AN: 60316

GnomAD4 genome AF: 0.0504 AC: 7677 AN: 152294 Hom.: 359 Cov.: 32 AF XY: 0.0515 AC XY: 3837 AN XY: 74462

African (AFR) AF: 0.118 AC: 4911 AN: 41554

American (AMR) AF: 0.0259 AC: 396 AN: 15302

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

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4828

European-Finnish (FIN) AF: 0.0668 AC: 709 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0184 AC: 1254 AN: 68024

Other (OTH) AF: 0.0407 AC: 86 AN: 2114

Alfa AF: 0.0314 Hom.: 60

Bravo AF: 0.0501

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.045
DANN	Benign	0.72
PhyloP100		-1.9
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: rs78405727; hg19: chr1-46655495;