rs12618769

Variant names:

• chr2-98623468-C-T
• rs12618769
• NM_012214.3:c.*2098G>A

Variant summary

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

The NM_012214.3(MGAT4A):​c.*2098G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 985,188 control chromosomes in the GnomAD database, including 12,630 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2614 hom., cov: 33)
  • Exomes 𝑓: 0.16 (10016 hom.)
• Consequence: MGAT4A NM_012214.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375

Genes affected

MGAT4A (HGNC:7047): (alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A) This gene encodes a key glycosyltransferase that regulates the formation of tri- and multiantennary branching structures in the Golgi apparatus. The encoded protein, in addition to the related isoenzyme B, catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc in a beta-1,4 linkage to the Man-alpha-1,3-Man-beta-1,4-GlcNAc arm of R-Man-alpha-1,6(GlcNAc-beta-1,2-Man-alpha-1,3)Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-Asn. The encoded protein may play a role in regulating the availability of serum glycoproteins, oncogenesis, and differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT4A	NM_012214.3	c.*2098G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000393487.6	NP_036346.1
MGAT4A	NM_001160154.2	c.1198-1963G>A		intron_variant	Intron 12 of 12		NP_001153626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT4A	ENST00000393487	c.*2098G>A		3_prime_UTR_variant	Exon 16 of 16	5	NM_012214.3	ENSP00000377127.1
MGAT4A	ENST00000264968	c.*2098G>A		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000264968.2
MGAT4A	ENST00000414521.6	c.1198-1963G>A		intron_variant	Intron 12 of 12	2		ENSP00000404889.2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26803 AN: 152028 Hom.: 2611 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0802

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.155 AC: 129409 AN: 833042 Hom.: 10016 Cov.: 31 AF XY: 0.157 AC XY: 60228 AN XY: 384674

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.0802

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.176 AC: 26836 AN: 152146 Hom.: 2614 Cov.: 33 AF XY: 0.173 AC XY: 12857 AN XY: 74364

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0796

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.183

Alfa AF: 0.162 Hom.: 3755

Bravo AF: 0.177

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.25

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: rs12618769; hg19: chr2-99239931;