rs12505221

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-140461967-A-C
• chr4-140461967-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001277353.2(MGAT4D):​c.724T>G​(p.Leu242Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33070546).

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>G	p.Leu242Val	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>G	p.Leu242Val	missense	Exon 7 of 11	ENSP00000421185.1	A6NG13
	MGAT4D	ENST00000503109.6	TSL:5	c.724T>G	p.Leu242Val	missense	Exon 7 of 11	ENSP00000426225.2	D6RH02
	MGAT4D	ENST00000515354.5	TSL:3	c.254-5248T>G		intron	N/A	ENSP00000423767.1	D6RCD3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.036
Eigen_PC	Benign	0.080
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.64	T
PhyloP100		4.8
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Vest4		0.29
MutPred		0.72		Loss of helix (P = 0.1706)
MVP		0.34
ClinPred		0.85	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.24
Mutation Taster		=99/1	polymorphism

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;