chr14-49620823-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_002408.4(MGAT2):c.-446C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 612,772 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00051 ( 3 hom. )

Consequence

MGAT2
NM_002408.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.601

Publications

0 publications found

Variant links:

Genes affected

MGAT2 (HGNC:7045): (alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase) The product of this gene is a Golgi enzyme catalyzing an essential step in the conversion of oligomannose to complex N-glycans. The enzyme has the typical glycosyltransferase domains: a short N-terminal cytoplasmic domain, a hydrophobic non-cleavable signal-anchor domain, and a C-terminal catalytic domain. Mutations in this gene may lead to carbohydrate-deficient glycoprotein syndrome, type II. The coding region of this gene is intronless. Transcript variants with a spliced 5' UTR may exist, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

MGAT2 links:

ENSG00000258377 (HGNC:):

ENSG00000258377 links:

RPL36AL (HGNC:10346): (ribosomal protein L36a like) Cytoplasmic ribosomes, organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein, which shares sequence similarity with yeast ribosomal protein L44, belongs to the L44E (L36AE) family of ribosomal proteins. This gene and the human gene officially named ribosomal protein L36a (RPL36A) encode nearly identical proteins; however, they are distinct genes. Although the name of this gene has been referred to as ribosomal protein L36a (RPL36A), its official name is ribosomal protein L36a-like (RPL36AL). As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL36AL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000558 (85/152318) while in subpopulation NFE AF = 0.000235 (16/68016). AF 95% confidence interval is 0.000147. There are 0 homozygotes in GnomAd4. There are 61 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002408.4. 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
	MGAT2	NM_002408.4	MANE Select	c.-446C>G		5_prime_UTR	Exon 1 of 1	NP_002399.1	Q10469
	RPL36AL	NM_001001.5	MANE Select	c.-298G>C		upstream_gene	N/A	NP_000992.1	Q969Q0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MGAT2	ENST00000305386.4	TSL:6 MANE Select	c.-446C>G	5_prime_UTR	Exon 1 of 1	ENSP00000307423.2	Q10469
ENSG00000258377	ENST00000555043.2	TSL:2	n.2461G>C	non_coding_transcript_exon	Exon 2 of 2
RPL36AL	ENST00000298289.7	TSL:1 MANE Select	c.-298G>C	upstream_gene	N/A	ENSP00000346012.5	Q969Q0

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000510

AC:

235

AN:

460454

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

115

AN XY:

245816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12008

American (AMR)

AF:

0.00

AC:

AN:

21352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14056

East Asian (EAS)

AF:

0.00

AC:

AN:

30174

South Asian (SAS)

AF:

0.00

AC:

AN:

48674

European-Finnish (FIN)

AF:

0.00634

AC:

189

AN:

29818

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2052

European-Non Finnish (NFE)

AF:

0.000127

AC:

AN:

275874

Other (OTH)

AF:

0.000416

AC:

AN:

26446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000558

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41590

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00631

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000741

Hom.:

Bravo

AF:

0.0000416

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

MGAT2-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.1

(source)

DANN

Benign

0.70

PhyloP100

-0.60

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over