rs776718727

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-76882219-C-G
• chr17-76882219-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001199172.2(MGAT5B):​c.250C>G​(p.Arg84Gly) 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 1,461,336 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R84C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MGAT5B NM_001199172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT5B	NM_001199172.2	c.250C>G	p.Arg84Gly	missense_variant	Exon 3 of 18	ENST00000569840.7	NP_001186101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT5B	ENST00000569840.7	c.250C>G	p.Arg84Gly	missense_variant	Exon 3 of 18	5	NM_001199172.2	ENSP00000456037.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248574 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134960

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461336 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.000111 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;T;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.9	L;L;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	D;D;D;N
REVEL	Uncertain	0.36
Sift	Benign	0.060	T;D;D;D
Sift4G	Benign	0.12	T;T;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.87
MutPred		0.49		Loss of MoRF binding (P = 0.0476);Loss of MoRF binding (P = 0.0476);Loss of MoRF binding (P = 0.0476);.;
MVP		0.77
MPC		1.3
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.60
gMVP		0.74

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

LitVar

Other links and lift over

dbSNP: rs776718727; hg19: chr17-74878301;