rs2292486

Variant names:

• chr1-46193238-G-A
• rs2292486
• NM_017739.4:c.1111-23C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-46193238-G-A
• chr1-46193238-G-C

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.1111-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,614,048 control chromosomes in the GnomAD database, including 5,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (473 hom., cov: 32)
  • Exomes 𝑓: 0.037 (5018 hom.)
• Consequence: POMGNT1 NM_017739.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.946
• Publications: 6 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=-0.81).
• BP6: Variant 1-46193238-G-A is Benign according to our data. Variant chr1-46193238-G-A is described in ClinVar as Benign. ClinVar VariationId is 260870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	NM_017739.4	MANE Select	c.1111-23C>T		intron	N/A	NP_060209.4	Q8WZA1-1
	POMGNT1	NM_001243766.2		c.1111-23C>T		intron	N/A	NP_001230695.2	Q8WZA1-2
	POMGNT1	NM_001410783.1		c.1111-23C>T		intron	N/A	NP_001397712.1	A0A8I5KNB7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	ENST00000371984.8	TSL:1 MANE Select	c.1111-23C>T		intron	N/A	ENSP00000361052.3	Q8WZA1-1
	POMGNT1	ENST00000371992.1	TSL:2	c.1111-23C>T		intron	N/A	ENSP00000361060.1	Q8WZA1-2
	POMGNT1	ENST00000692369.1		c.1111-23C>T		intron	N/A	ENSP00000508453.1	A0A8I5KNB7

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5658 AN: 152146 Hom.: 470 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0372

GnomAD2 exomes AF: 0.0673 AC: 16886 AN: 251078 AF XY: 0.0720

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.0451

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.336

Gnomad FIN exome AF: 0.0175

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0485

GnomAD4 exome AF: 0.0375 AC: 54750 AN: 1461784 Hom.: 5018 Cov.: 33 AF XY: 0.0421 AC XY: 30645 AN XY: 727178

African (AFR) AF: 0.0255 AC: 853 AN: 33480

American (AMR) AF: 0.0418 AC: 1867 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0114 AC: 297 AN: 26132

East Asian (EAS) AF: 0.368 AC: 14597 AN: 39672

South Asian (SAS) AF: 0.200 AC: 17226 AN: 86224

European-Finnish (FIN) AF: 0.0176 AC: 942 AN: 53414

Middle Eastern (MID) AF: 0.0369 AC: 213 AN: 5766

European-Non Finnish (NFE) AF: 0.0144 AC: 16015 AN: 1111988

Other (OTH) AF: 0.0454 AC: 2740 AN: 60396

GnomAD4 genome AF: 0.0372 AC: 5663 AN: 152264 Hom.: 473 Cov.: 32 AF XY: 0.0428 AC XY: 3188 AN XY: 74432

African (AFR) AF: 0.0242 AC: 1006 AN: 41556

American (AMR) AF: 0.0344 AC: 527 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.345 AC: 1778 AN: 5156

South Asian (SAS) AF: 0.217 AC: 1044 AN: 4820

European-Finnish (FIN) AF: 0.0153 AC: 162 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 979 AN: 68024

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0275 Hom.: 486

Bravo AF: 0.0355

Asia WGS AF: 0.252 AC: 874 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (1)
-	-	1	not specified (1)
-	-	1	Retinitis pigmentosa 76 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		0.95
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: rs2292486; hg19: chr1-46658910; COSMIC: COSV64341385; COSMIC: COSV64341385;