chr4-140461967-A-T

Variant names:

• chr4-140461967-A-T
• rs12505221
• NM_001277353.2:c.724T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277353.2(MGAT4D):​c.724T>A​(p.Leu242Met) variant causes a missense change. The variant allele was found at a frequency of 0.259 in 699,112 control chromosomes in the GnomAD database, including 24,910 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4902 hom., cov: 30)
  • Exomes 𝑓: 0.26 (20008 hom.)
• Consequence: MGAT4D NM_001277353.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75
• Publications: 7 publications found

Genes affected

MGAT4D (HGNC:43619): (MGAT4 family member D) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein N-linked glycosylation. Predicted to be located in membrane. Predicted to be active in Golgi stack; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0064281523).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277353.2. 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
	MGAT4D	NM_001277353.2	MANE Select	c.724T>A	p.Leu242Met	missense	Exon 7 of 11	NP_001264282.1	A6NG13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT4D	ENST00000511113.6	TSL:5 MANE Select	c.724T>A	p.Leu242Met	missense	Exon 7 of 11	ENSP00000421185.1	A6NG13
	MGAT4D	ENST00000503109.6	TSL:5	c.724T>A	p.Leu242Met	missense	Exon 7 of 11	ENSP00000426225.2	D6RH02
	MGAT4D	ENST00000515354.5	TSL:3	c.254-5248T>A		intron	N/A	ENSP00000423767.1	D6RCD3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38061 AN: 151610 Hom.: 4905 Cov.: 30

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.257

GnomAD2 exomes AF: 0.287 AC: 38454 AN: 133848 AF XY: 0.290

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.277

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.262 AC: 143296 AN: 547386 Hom.: 20008 Cov.: 0 AF XY: 0.267 AC XY: 79219 AN XY: 296350

African (AFR) AF: 0.244 AC: 3841 AN: 15758

American (AMR) AF: 0.364 AC: 12583 AN: 34574

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 5949 AN: 19926

East Asian (EAS) AF: 0.251 AC: 8012 AN: 31976

South Asian (SAS) AF: 0.363 AC: 22495 AN: 61962

European-Finnish (FIN) AF: 0.224 AC: 7487 AN: 33458

Middle Eastern (MID) AF: 0.282 AC: 1147 AN: 4064

European-Non Finnish (NFE) AF: 0.235 AC: 74061 AN: 315258

Other (OTH) AF: 0.254 AC: 7721 AN: 30410

GnomAD4 genome AF: 0.251 AC: 38076 AN: 151726 Hom.: 4902 Cov.: 30 AF XY: 0.256 AC XY: 18977 AN XY: 74154

African (AFR) AF: 0.235 AC: 9735 AN: 41344

American (AMR) AF: 0.319 AC: 4861 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1468 AN: 5160

South Asian (SAS) AF: 0.376 AC: 1804 AN: 4794

European-Finnish (FIN) AF: 0.236 AC: 2480 AN: 10502

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15828 AN: 67906

Other (OTH) AF: 0.257 AC: 541 AN: 2108

Alfa AF: 0.252 Hom.: 985

Bravo AF: 0.256

TwinsUK AF: 0.231 AC: 857

ALSPAC AF: 0.234 AC: 903

ExAC AF: 0.276 AC: 4181

Asia WGS AF: 0.340 AC: 1181 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.11
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	2.8	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.14
ClinPred		0.0092	T
GERP RS		4.6
Varity_R		0.055
gMVP		0.24
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12505221; hg19: chr4-141383121; COSMIC: COSV72331872; COSMIC: COSV72331872;