rs115804669

Variant names:

• chr1-46193964-C-G
• rs115804669
• NM_017739.4:c.880-39G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-46193964-C-G
• chr1-46193964-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017739.4(POMGNT1):​c.880-39G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,610,962 control chromosomes in the GnomAD database, including 545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (76 hom., cov: 33)
  • Exomes 𝑓: 0.021 (469 hom.)
• Consequence: POMGNT1 NM_017739.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.912

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=-0.84).
• BP6: Variant 1-46193964-C-G is Benign according to our data. Variant chr1-46193964-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-46193964-C-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0281 (4279/152278) while in subpopulation SAS AF = 0.0433 (209/4822). AF 95% confidence interval is 0.0392. There are 76 homozygotes in GnomAd4. There are 2278 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMGNT1	NM_017739.4	c.880-39G>C		intron_variant	Intron 9 of 21	ENST00000371984.8	NP_060209.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT1	ENST00000371984.8	c.880-39G>C		intron_variant	Intron 9 of 21	1	NM_017739.4	ENSP00000361052.3

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4273 AN: 152160 Hom.: 76 Cov.: 33

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.0258 AC: 6330 AN: 245278 AF XY: 0.0268

Gnomad AFR exome AF: 0.0435

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.000830

Gnomad FIN exome AF: 0.0646

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0247

GnomAD4 exome AF: 0.0210 AC: 30592 AN: 1458684 Hom.: 469 Cov.: 35 AF XY: 0.0217 AC XY: 15764 AN XY: 725246

Gnomad4 AFR exome AF: 0.0442 AC: 1478 AN: 33454

Gnomad4 AMR exome AF: 0.0105 AC: 464 AN: 44186

Gnomad4 ASJ exome AF: 0.0297 AC: 771 AN: 25990

Gnomad4 EAS exome AF: 0.000555 AC: 22 AN: 39652

Gnomad4 SAS exome AF: 0.0439 AC: 3756 AN: 85482

Gnomad4 FIN exome AF: 0.0609 AC: 3246 AN: 53270

Gnomad4 NFE exome AF: 0.0174 AC: 19349 AN: 1110570

Gnomad4 Remaining exome AF: 0.0228 AC: 1375 AN: 60316

GnomAD4 genome AF: 0.0281 AC: 4279 AN: 152278 Hom.: 76 Cov.: 33 AF XY: 0.0306 AC XY: 2278 AN XY: 74462

Gnomad4 AFR AF: 0.0408 AC: 0.0408404 AN: 0.0408404

Gnomad4 AMR AF: 0.0173 AC: 0.0173203 AN: 0.0173203

Gnomad4 ASJ AF: 0.0311 AC: 0.0311239 AN: 0.0311239

Gnomad4 EAS AF: 0.00135 AC: 0.00134979 AN: 0.00134979

Gnomad4 SAS AF: 0.0433 AC: 0.043343 AN: 0.043343

Gnomad4 FIN AF: 0.0670 AC: 0.066987 AN: 0.066987

Gnomad4 NFE AF: 0.0180 AC: 0.0179811 AN: 0.0179811

Gnomad4 OTH AF: 0.0227 AC: 0.0227058 AN: 0.0227058

Alfa AF: 0.0242 Hom.: 9

Bravo AF: 0.0240

Asia WGS AF: 0.0270 AC: 93 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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs115804669; hg19: chr1-46659636;