17-76882219-C-T

Variant names:

• chr17-76882219-C-T
• rs776718727
• NM_001199172.2:c.250C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001199172.2(MGAT5B):​c.250C>T​(p.Arg84Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,336 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R84H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MGAT5B NM_001199172.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199172.2. 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
	MGAT5B	NM_001199172.2	MANE Select	c.250C>T	p.Arg84Cys	missense	Exon 3 of 18	NP_001186101.1	Q3V5L5-1
	MGAT5B	NM_198955.1		c.283C>T	p.Arg95Cys	missense	Exon 2 of 16	NP_945193.1	Q3V5L5-2
	MGAT5B	NM_144677.3		c.250C>T	p.Arg84Cys	missense	Exon 3 of 17	NP_653278.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT5B	ENST00000569840.7	TSL:5 MANE Select	c.250C>T	p.Arg84Cys	missense	Exon 3 of 18	ENSP00000456037.2	Q3V5L5-1
	MGAT5B	ENST00000428789.6	TSL:1	c.283C>T	p.Arg95Cys	missense	Exon 2 of 16	ENSP00000391227.2	Q3V5L5-2
	MGAT5B	ENST00000565675.1	TSL:1	c.250C>T	p.Arg84Cys	missense	Exon 3 of 3	ENSP00000457614.1	H3BR20

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248574 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461336 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727004

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111896

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

Alfa AF: 0.000111 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.53		Gain of methylation at K83 (P = 0.0143)
MVP		0.79
MPC		1.3
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.28
gMVP		0.72
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs776718727; hg19: chr17-74878301;