rs12618769

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT4A	NM_012214.3	MANE Select	c.*2098G>A		3_prime_UTR	Exon 16 of 16	NP_036346.1
	MGAT4A	NM_001160154.2		c.1198-1963G>A		intron	N/A	NP_001153626.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT4A	ENST00000393487.6	TSL:5 MANE Select	c.*2098G>A		3_prime_UTR	Exon 16 of 16	ENSP00000377127.1
	MGAT4A	ENST00000264968.7	TSL:1	c.*2098G>A		3_prime_UTR	Exon 15 of 15	ENSP00000264968.2
	MGAT4A	ENST00000414521.6	TSL:2	c.1198-1963G>A		intron	N/A	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

African (AFR) AF: 0.250 AC: 3951 AN: 15782

American (AMR) AF: 0.131 AC: 129 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 1251 AN: 5152

East Asian (EAS) AF: 0.0802 AC: 291 AN: 3630

South Asian (SAS) AF: 0.137 AC: 2254 AN: 16456

European-Finnish (FIN) AF: 0.141 AC: 39 AN: 276

Middle Eastern (MID) AF: 0.164 AC: 266 AN: 1620

European-Non Finnish (NFE) AF: 0.154 AC: 116991 AN: 761844

Other (OTH) AF: 0.155 AC: 4237 AN: 27298

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

African (AFR) AF: 0.248 AC: 10290 AN: 41472

American (AMR) AF: 0.121 AC: 1851 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 865 AN: 3466

East Asian (EAS) AF: 0.0796 AC: 412 AN: 5176

South Asian (SAS) AF: 0.138 AC: 668 AN: 4828

European-Finnish (FIN) AF: 0.152 AC: 1609 AN: 10578

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10587 AN: 68016

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.163 Hom.: 8251

Bravo AF: 0.177

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs12618769; hg19: chr2-99239931;