chr5-180792304-C-T

Variant names:

• chr5-180792304-C-T
• rs7726005
• NM_002406.4:c.668G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002406.4(MGAT1):​c.668G>A​(p.Arg223Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,609,498 control chromosomes in the GnomAD database, including 8,981 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1446 hom., cov: 33)
  • Exomes 𝑓: 0.095 (7535 hom.)
• Consequence: MGAT1 NM_002406.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

Genes affected

MGAT1 (HGNC:7044): (alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase) There are believed to be over 100 different glycosyltransferases involved in the synthesis of protein-bound and lipid-bound oligosaccharides. UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I is a medial-Golgi enzyme essential for the synthesis of hybrid and complex N-glycans. The protein, encoded by a single exon, shows typical features of a type II transmembrane protein. The protein is believed to be essential for normal embryogenesis. Several variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017002821).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT1	NM_002406.4	c.668G>A	p.Arg223Gln	missense_variant	Exon 2 of 2	ENST00000307826.5	NP_002397.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT1	ENST00000307826.5	c.668G>A	p.Arg223Gln	missense_variant	Exon 2 of 2	1	NM_002406.4	ENSP00000311888.4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19317 AN: 152132 Hom.: 1433 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.112 AC: 27428 AN: 245866 Hom.: 1907 AF XY: 0.113 AC XY: 15138 AN XY: 133812

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.0687

Gnomad ASJ exome AF: 0.0731

Gnomad EAS exome AF: 0.230

Gnomad SAS exome AF: 0.158

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0835

Gnomad OTH exome AF: 0.0978

GnomAD4 exome AF: 0.0950 AC: 138390 AN: 1457248 Hom.: 7535 Cov.: 36 AF XY: 0.0967 AC XY: 69996 AN XY: 724150

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.0715

Gnomad4 ASJ exome AF: 0.0759

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0832

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.127 AC: 19381 AN: 152250 Hom.: 1446 Cov.: 33 AF XY: 0.129 AC XY: 9628 AN XY: 74446

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0849

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0892 Hom.: 1641

Bravo AF: 0.129

TwinsUK AF: 0.0839 AC: 311

ALSPAC AF: 0.0851 AC: 328

ESP6500AA AF: 0.200 AC: 877

ESP6500EA AF: 0.0797 AC: 684

ExAC AF: 0.114 AC: 13841

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.29	T;T;T;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.47	.;.;.;T;.
MetaRNN	Benign	0.0017	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.28	N;N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.12	N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.63	T;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.019
MPC		0.91
ClinPred		0.0082	T
GERP RS		5.6
Varity_R		0.026
gMVP		0.28

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: rs7726005; hg19: chr5-180219304; COSMIC: COSV57133090; COSMIC: COSV57133090;