rs12505221

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/18 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT4D	NM_001277353.2	c.724T>G	p.Leu242Val	missense_variant	7/11	ENST00000511113.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT4D	ENST00000511113.6	c.724T>G	p.Leu242Val	missense_variant	7/11	5	NM_001277353.2	P4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.64	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0060	D;D
Vest4		0.29
MutPred		0.72		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.34
ClinPred		0.85	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs12505221; hg19: chr4-141383121;