dbSNP rs191831149: MGAT5B:p.Thr19Met (chr17-76872805-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198955.1(MGAT5B):c.56C>T(p.Thr19Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 1,614,078 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 36 hom. )

Consequence

MGAT5B
NM_198955.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.100

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034640431).

BP6

Variant 17-76872805-C-T is Benign according to our data. Variant chr17-76872805-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2648321.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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.69-46C>T		intron	N/A	NP_001186101.1	Q3V5L5-1
MGAT5B	NM_198955.1		c.56C>T	p.Thr19Met	missense	Exon 1 of 16	NP_945193.1	Q3V5L5-2
MGAT5B	NM_144677.3		c.69-46C>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.56C>T	p.Thr19Met	missense	Exon 1 of 16	ENSP00000391227.2	Q3V5L5-2
MGAT5B	ENST00000569840.7	TSL:5 MANE Select	c.69-46C>T		intron	N/A	ENSP00000456037.2	Q3V5L5-1
MGAT5B	ENST00000565675.1	TSL:1	c.69-46C>T		intron	N/A	ENSP00000457614.1	H3BR20

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

647

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00623

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00471

AC:

1176

AN:

249816

AF XY:

0.00466

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00671

GnomAD4 exome

AF:

0.00524

AC:

7661

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

3809

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.00158

AC:

AN:

33474

American (AMR)

AF:

0.00268

AC:

120

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

608

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00203

AC:

175

AN:

86252

European-Finnish (FIN)

AF:

0.00223

AC:

119

AN:

53384

Middle Eastern (MID)

AF:

0.00919

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00554

AC:

6162

AN:

1111948

Other (OTH)

AF:

0.00613

AC:

370

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

476

952

1428

1904

2380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<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:

0.00425

AC:

648

AN:

152350

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41578

American (AMR)

AF:

0.00111

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00235

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00623

AC:

424

AN:

68042

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00609

Hom.:

Bravo

AF:

0.00433

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00436

AC:

529

EpiCase

AF:

0.00840

EpiControl

AF:

0.00771

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.9

(source)

DANN

Benign

0.96

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

PhyloP100

-0.10

PROVEAN

Benign

-0.11

REVEL

Benign

0.012

Sift

Uncertain

0.010

Sift4G

Uncertain

0.025

Polyphen

0.0050

Vest4

0.078

MVP

0.076

MPC

0.35

ClinPred

0.0070

GERP RS

-1.5

PromoterAI

-0.071

Neutral

(source)

gMVP

0.28

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

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