NM_032806.6:c.-43C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_032806.6(POMGNT2):c.-43C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,461,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 0 hom. )

Consequence

POMGNT2
NM_032806.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.605

Publications

6 publications found

Variant links:

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]

POMGNT2 Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
myopathy caused by variation in POMGNT2
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POMGNT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-43081474-G-T is Benign according to our data. Variant chr3-43081474-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 512428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000671 (102/152100) while in subpopulation AMR AF = 0.00203 (31/15286). AF 95% confidence interval is 0.00147. There are 0 homozygotes in GnomAd4. There are 42 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
POMGNT2	NM_032806.6 link	c.-43C>A	5_prime_UTR_variant	Exon 2 of 2	ENST00000344697.3	NP_116195.2	Q8NAT1A0A024R2P4
POMGNT2	NM_001437285.1 link	c.-43C>A	5_prime_UTR_variant	Exon 3 of 3		NP_001424214.1
POMGNT2	XM_011534163.3 link	c.-43C>A	5_prime_UTR_variant	Exon 3 of 3		XP_011532465.1	Q8NAT1A0A024R2P4
POMGNT2	XM_017007353.2 link	c.-43C>A	5_prime_UTR_variant	Exon 4 of 4		XP_016862842.1	Q8NAT1A0A024R2P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT2	ENST00000344697.3 link	c.-43C>A		5_prime_UTR_variant	Exon 2 of 2	1	NM_032806.6	ENSP00000344125.2		Q8NAT1

Frequencies

GnomAD3 genomes

AF:

0.000665

AC:

101

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000868

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000478

AC:

AN:

102478

AF XY:

0.000527

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000797

Gnomad OTH exome

AF:

0.000720

GnomAD4 exome

AF:

0.000809

AC:

1059

AN:

1309314

Hom.:

Cov.:

AF XY:

0.000813

AC XY:

519

AN XY:

638094

show subpopulations

African (AFR)

AF:

0.0000346

AC:

AN:

28926

American (AMR)

AF:

0.000702

AC:

AN:

24216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35756

South Asian (SAS)

AF:

0.00130

AC:

AN:

66138

European-Finnish (FIN)

AF:

0.0000227

AC:

AN:

43964

Middle Eastern (MID)

AF:

0.000433

AC:

AN:

4620

European-Non Finnish (NFE)

AF:

0.000890

AC:

919

AN:

1032130

Other (OTH)

AF:

0.000591

AC:

AN:

54184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000671

AC:

102

AN:

152100

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41488

American (AMR)

AF:

0.00203

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000868

AC:

AN:

67984

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000142

Hom.:

21791

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 12, 2017

GeneDx

Significance:Likely 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:Likely 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

-0.81

CADD

Benign

9.7

(source)

DANN

Benign

0.76

PhyloP100

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over