17-76872936-G-C

Variant names:

• chr17-76872936-G-C
• rs749963645
• NM_001199172.2:c.154G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001199172.2(MGAT5B):​c.154G>C​(p.Asp52His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D52N) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: MGAT5B NM_001199172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.45
• Publications: 2 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

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.154G>C	p.Asp52His	missense	Exon 2 of 18	NP_001186101.1	Q3V5L5-1
	MGAT5B	NM_198955.1		c.187G>C	p.Asp63His	missense	Exon 1 of 16	NP_945193.1	Q3V5L5-2
	MGAT5B	NM_144677.3		c.154G>C	p.Asp52His	missense	Exon 2 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.154G>C	p.Asp52His	missense	Exon 2 of 18	ENSP00000456037.2	Q3V5L5-1
	MGAT5B	ENST00000428789.6	TSL:1	c.187G>C	p.Asp63His	missense	Exon 1 of 16	ENSP00000391227.2	Q3V5L5-2
	MGAT5B	ENST00000565675.1	TSL:1	c.154G>C	p.Asp52His	missense	Exon 2 of 3	ENSP00000457614.1	H3BR20

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.28		Loss of solvent accessibility (P = 0.0169)
MVP		0.84
MPC		1.2
ClinPred		0.98	D
GERP RS		4.7
PromoterAI		0.010	Neutral
Varity_R		0.53
gMVP		0.81

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: rs749963645; hg19: chr17-74869018;