rs112610756

Variant names:

• chr1-46189808-G-A
• rs112610756
• NM_017739.4:c.1785+46C>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.1785+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,612,112 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (27 hom.)
• Consequence: POMGNT1 NM_017739.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.06
• Publications: 1 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=-0.78).
• BP6: Variant 1-46189808-G-A is Benign according to our data. Variant chr1-46189808-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 260872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00953 (1452/152370) while in subpopulation AFR AF = 0.0325 (1351/41590). AF 95% confidence interval is 0.031. There are 29 homozygotes in GnomAd4. There are 709 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 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.1785+46C>T		intron	N/A	NP_060209.4
	POMGNT1	NM_001243766.2		c.1785+46C>T		intron	N/A	NP_001230695.2
	POMGNT1	NM_001410783.1		c.1785+46C>T		intron	N/A	NP_001397712.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT1	ENST00000371984.8	TSL:1 MANE Select	c.1785+46C>T		intron	N/A	ENSP00000361052.3
	POMGNT1	ENST00000371992.1	TSL:2	c.1785+46C>T		intron	N/A	ENSP00000361060.1
	POMGNT1	ENST00000692369.1		c.1785+46C>T		intron	N/A	ENSP00000508453.1

Frequencies

GnomAD3 genomes AF: 0.00942 AC: 1434 AN: 152252 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00256 AC: 631 AN: 246854 AF XY: 0.00189

Gnomad AFR exome AF: 0.0347

Gnomad AMR exome AF: 0.00146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.00169

GnomAD4 exome AF: 0.00105 AC: 1526 AN: 1459742 Hom.: 27 Cov.: 33 AF XY: 0.000864 AC XY: 627 AN XY: 725912

African (AFR) AF: 0.0346 AC: 1158 AN: 33460

American (AMR) AF: 0.00189 AC: 84 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.000199 AC: 17 AN: 85566

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53358

Middle Eastern (MID) AF: 0.00241 AC: 13 AN: 5404

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111546

Other (OTH) AF: 0.00317 AC: 191 AN: 60288

GnomAD4 genome AF: 0.00953 AC: 1452 AN: 152370 Hom.: 29 Cov.: 32 AF XY: 0.00952 AC XY: 709 AN XY: 74512

African (AFR) AF: 0.0325 AC: 1351 AN: 41590

American (AMR) AF: 0.00438 AC: 67 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68040

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00540 Hom.: 1

Bravo AF: 0.0108

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.97
DANN	Benign	0.57
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs112610756; hg19: chr1-46655480;