chr1-46190800-G-A

Variant names:

• chr1-46190800-G-A
• rs10493123
• NM_017739.4:c.1540-16C>T

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.1540-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,603,762 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (79 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (97 hom.)
• Consequence: POMGNT1 NM_001243766.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.259
• 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=-0.75).
• BP6: Variant 1-46190800-G-A is Benign according to our data. Variant chr1-46190800-G-A is described in ClinVar as Benign. ClinVar VariationId is 162587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0608 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	NM_017739.4	MANE Select	c.1540-16C>T		intron	N/A	NP_060209.4
	POMGNT1	NM_001243766.2		c.1540-16C>T		intron	N/A	NP_001230695.2
	POMGNT1	NM_001410783.1		c.1540-16C>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.1540-16C>T		intron	N/A	ENSP00000361052.3
	POMGNT1	ENST00000371992.1	TSL:2	c.1540-16C>T		intron	N/A	ENSP00000361060.1
	POMGNT1	ENST00000692369.1		c.1540-16C>T		intron	N/A	ENSP00000508453.1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2837 AN: 152152 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00612 AC: 1540 AN: 251468 AF XY: 0.00480

Gnomad AFR exome AF: 0.0674

Gnomad AMR exome AF: 0.00457

Gnomad ASJ exome AF: 0.0178

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00252 AC: 3661 AN: 1451492 Hom.: 97 Cov.: 30 AF XY: 0.00226 AC XY: 1636 AN XY: 722768

African (AFR) AF: 0.0656 AC: 2178 AN: 33216

American (AMR) AF: 0.00481 AC: 215 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 489 AN: 26078

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39662

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00627 AC: 36 AN: 5740

European-Non Finnish (NFE) AF: 0.000319 AC: 352 AN: 1102568

Other (OTH) AF: 0.00641 AC: 385 AN: 60100

GnomAD4 genome AF: 0.0187 AC: 2844 AN: 152270 Hom.: 79 Cov.: 32 AF XY: 0.0181 AC XY: 1349 AN XY: 74448

African (AFR) AF: 0.0628 AC: 2609 AN: 41544

American (AMR) AF: 0.00726 AC: 111 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68022

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.0112 Hom.: 24

Bravo AF: 0.0212

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3;C3150417:Autosomal recessive limb-girdle muscular dystrophy type 2O (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.70
PhyloP100		0.26
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: rs10493123; hg19: chr1-46656472; COSMIC: COSV107458774; COSMIC: COSV107458774;