rs7527668

Variant names:

• chr1-46193432-T-C
• rs7527668
• NM_017739.4:c.1027-44A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-46193432-T-C
• chr1-46193432-T-G

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.1027-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,602,566 control chromosomes in the GnomAD database, including 105,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11099 hom., cov: 33)
  • Exomes 𝑓: 0.36 (94621 hom.)
• Consequence: POMGNT1 NM_017739.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.303
• Publications: 14 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 1-46193432-T-C is Benign according to our data. Variant chr1-46193432-T-C is described in ClinVar as Benign. ClinVar VariationId is 260869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMGNT1	NM_017739.4	c.1027-44A>G		intron_variant	Intron 11 of 21	ENST00000371984.8	NP_060209.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT1	ENST00000371984.8	c.1027-44A>G		intron_variant	Intron 11 of 21	1	NM_017739.4	ENSP00000361052.3

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57311 AN: 151934 Hom.: 11081 Cov.: 33

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.363

GnomAD2 exomes AF: 0.365 AC: 84019 AN: 230100 AF XY: 0.367

Gnomad AFR exome AF: 0.447

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.358 AC: 518812 AN: 1450514 Hom.: 94621 Cov.: 74 AF XY: 0.360 AC XY: 259664 AN XY: 720432

African (AFR) AF: 0.459 AC: 15323 AN: 33396

American (AMR) AF: 0.393 AC: 16550 AN: 42132

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 8446 AN: 25884

East Asian (EAS) AF: 0.157 AC: 6201 AN: 39508

South Asian (SAS) AF: 0.449 AC: 38152 AN: 84932

European-Finnish (FIN) AF: 0.395 AC: 20838 AN: 52808

Middle Eastern (MID) AF: 0.391 AC: 2234 AN: 5720

European-Non Finnish (NFE) AF: 0.353 AC: 390018 AN: 1106066

Other (OTH) AF: 0.350 AC: 21050 AN: 60068

GnomAD4 genome AF: 0.377 AC: 57398 AN: 152052 Hom.: 11099 Cov.: 33 AF XY: 0.379 AC XY: 28168 AN XY: 74340

African (AFR) AF: 0.446 AC: 18480 AN: 41444

American (AMR) AF: 0.373 AC: 5710 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3470

East Asian (EAS) AF: 0.160 AC: 825 AN: 5150

South Asian (SAS) AF: 0.435 AC: 2099 AN: 4822

European-Finnish (FIN) AF: 0.384 AC: 4068 AN: 10598

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24018 AN: 67960

Other (OTH) AF: 0.365 AC: 771 AN: 2110

Alfa AF: 0.359 Hom.: 13509

Bravo AF: 0.375

Asia WGS AF: 0.294 AC: 1025 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2O Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 76 Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: 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	-0.89
CADD	Benign	6.6
DANN	Benign	0.45
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7527668; hg19: chr1-46659104; COSMIC: COSV64339664; COSMIC: COSV64339664;