rs111777493

Variant names:

• chr3-43079687-C-T
• rs111777493
• NM_032806.6:c.*2G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032806.6(POMGNT2):​c.*2G>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 0.00211 in 1,608,040 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (42 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (33 hom.)
• Consequence: POMGNT2 NM_032806.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.48

Genes affected

POMGNT2 (HGNC:25902): (protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-)) This gene encodes a protein with glycosyltransferase activity although its function is not currently known. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-43079687-C-T is Benign according to our data. Variant chr3-43079687-C-T is described in ClinVar as [Benign]. Clinvar id is 385243.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 = 0.0109 (1658/152332) while in subpopulation AFR AF= 0.0375 (1559/41574). AF 95% confidence interval is 0.036. There are 42 homozygotes in gnomad4. There are 790 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMGNT2	NM_032806.6	c.*2G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000344697.3	NP_116195.2
POMGNT2	XM_005265515.4	c.*2G>A		3_prime_UTR_variant	Exon 3 of 3		XP_005265572.1
POMGNT2	XM_011534163.3	c.*2G>A		3_prime_UTR_variant	Exon 3 of 3		XP_011532465.1
POMGNT2	XM_017007353.2	c.*2G>A		3_prime_UTR_variant	Exon 4 of 4		XP_016862842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT2	ENST00000344697	c.*2G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_032806.6	ENSP00000344125.2

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1654 AN: 152214 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00311 AC: 767 AN: 246286 Hom.: 19 AF XY: 0.00220 AC XY: 293 AN XY: 132908

Gnomad AFR exome AF: 0.0406

Gnomad AMR exome AF: 0.00213

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000126

Gnomad OTH exome AF: 0.00249

GnomAD4 exome AF: 0.00119 AC: 1733 AN: 1455708 Hom.: 33 Cov.: 29 AF XY: 0.00103 AC XY: 747 AN XY: 723552

Gnomad4 AFR exome AF: 0.0404

Gnomad4 AMR exome AF: 0.00245

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000424

Gnomad4 OTH exome AF: 0.00321

GnomAD4 genome AF: 0.0109 AC: 1658 AN: 152332 Hom.: 42 Cov.: 33 AF XY: 0.0106 AC XY: 790 AN XY: 74488

Gnomad4 AFR AF: 0.0375

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00588 Hom.: 5

Bravo AF: 0.0124

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 05, 2016

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 provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.012
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs111777493; hg19: chr3-43121179;