Genetic Variant MGAT5B:p.Ala21Val (chr17-76872811-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198955.1(MGAT5B):c.62C>T(p.Ala21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A21G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MGAT5B
NM_198955.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.798

Publications

0 publications found

Variant links:

Genes affected

MGAT5B (HGNC:24140): (alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B) Enables alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase activity and manganese ion binding activity. Involved in protein O-linked glycosylation via serine. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

MGAT5B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039370745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198955.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MGAT5B	NM_001199172.2	MANE Select	c.69-40C>T		intron	N/A	NP_001186101.1	Q3V5L5-1
MGAT5B	NM_198955.1		c.62C>T	p.Ala21Val	missense	Exon 1 of 16	NP_945193.1	Q3V5L5-2
MGAT5B	NM_144677.3		c.69-40C>T		intron	N/A	NP_653278.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MGAT5B	ENST00000428789.6	TSL:1	c.62C>T	p.Ala21Val	missense	Exon 1 of 16	ENSP00000391227.2	Q3V5L5-2
MGAT5B	ENST00000569840.7	TSL:5 MANE Select	c.69-40C>T		intron	N/A	ENSP00000456037.2	Q3V5L5-1
MGAT5B	ENST00000565675.1	TSL:1	c.69-40C>T		intron	N/A	ENSP00000457614.1	H3BR20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111952

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.82

(source)

DANN

Benign

0.78

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.41

M_CAP

Benign

0.027

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

PhyloP100

-0.80

PROVEAN

Benign

0.34

REVEL

Benign

0.092

Sift

Benign

0.50

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.035

MutPred

0.22

Loss of glycosylation at P23 (P = 0.2461)

MVP

0.030

MPC

0.34

ClinPred

0.029

GERP RS

-3.6

PromoterAI

-0.098

Neutral

(source)

gMVP

0.50

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over