12-85979395-C-T

Position:

• chr12-85979395-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001351288.2(MGAT4C):​c.1331G>A​(p.Gly444Asp) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGAT4C NM_001351288.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.26

Genes affected

MGAT4C (HGNC:30871): (MGAT4 family member C) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein N-linked glycosylation. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055054754).
• BP6: Variant 12-85979395-C-T is Benign according to our data. Variant chr12-85979395-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2292228.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT4C	NM_001351288.2	c.1331G>A	p.Gly444Asp	missense_variant	5/5	ENST00000611864.5	NP_001338217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGAT4C	ENST00000611864.5	c.1331G>A	p.Gly444Asp	missense_variant	5/5	5	NM_001351288.2	ENSP00000481096	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.46
DEOGEN2	Benign	0.12	T;T;T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.35	N
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.055	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.98	N;N;N;N;N
MutationTaster	Benign	0.86	N;N;N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.22	.;.;N;.;N
REVEL	Benign	0.033
Sift	Benign	0.62	.;.;T;.;T
Sift4G	Benign	0.66	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.044
MVP		0.076
ClinPred		0.23	T
GERP RS		3.3
Varity_R		0.046
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-86373173;