rs181362801

Variant names:

• chr1-46189049-C-T
• rs181362801
• NM_017739.4:c.*221G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BS1 BS2

The NM_017739.4(POMGNT1):​c.*221G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,539,064 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (27 hom.)
• Consequence: POMGNT1 NM_017739.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 1.93
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-46189049-C-T is Benign according to our data. Variant chr1-46189049-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 876536.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00349 (532/152336) while in subpopulation NFE AF = 0.00463 (315/68024). AF 95% confidence interval is 0.00421. There are 1 homozygotes in GnomAd4. There are 275 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 27 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	NM_017739.4	MANE Select	c.*221G>A		3_prime_UTR	Exon 22 of 22	NP_060209.4	Q8WZA1-1
	POMGNT1	NM_001437653.1		c.*221G>A		3_prime_UTR	Exon 22 of 22	NP_001424582.1
	POMGNT1	NM_001438689.1		c.*221G>A		3_prime_UTR	Exon 22 of 22	NP_001425618.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	ENST00000371984.8	TSL:1 MANE Select	c.*221G>A		3_prime_UTR	Exon 22 of 22	ENSP00000361052.3	Q8WZA1-1
	POMGNT1	ENST00000908470.1		c.*221G>A		3_prime_UTR	Exon 22 of 22	ENSP00000578529.1
	POMGNT1	ENST00000687149.1		c.*221G>A		3_prime_UTR	Exon 21 of 21	ENSP00000509745.1	A0A8I5KVA5

Frequencies

GnomAD3 genomes AF: 0.00349 AC: 532 AN: 152218 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00463

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00238 AC: 3307 AN: 1386728 Hom.: 27 Cov.: 30 AF XY: 0.00248 AC XY: 1693 AN XY: 682922

African (AFR) AF: 0.0000966 AC: 3 AN: 31042

American (AMR) AF: 0.000410 AC: 14 AN: 34138

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 295 AN: 21872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39040

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74280

European-Finnish (FIN) AF: 0.0163 AC: 719 AN: 44166

Middle Eastern (MID) AF: 0.00157 AC: 7 AN: 4472

European-Non Finnish (NFE) AF: 0.00195 AC: 2102 AN: 1080534

Other (OTH) AF: 0.00290 AC: 166 AN: 57184

GnomAD4 genome AF: 0.00349 AC: 532 AN: 152336 Hom.: 1 Cov.: 32 AF XY: 0.00369 AC XY: 275 AN XY: 74490

African (AFR) AF: 0.000168 AC: 7 AN: 41584

American (AMR) AF: 0.000522 AC: 8 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0140 AC: 149 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00463 AC: 315 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00752 Hom.: 1

Bravo AF: 0.00209

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal recessive limb-girdle muscular dystrophy type 2O (1)
-	1	-	Congenital Muscular Dystrophy, alpha-dystroglycan related (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		1.9
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism

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: rs181362801; hg19: chr1-46654721;