2-98655513-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012214.3(MGAT4A):c.706A>G(p.Thr236Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00964 in 1,608,174 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (93 hom.)
• Consequence: MGAT4A NM_012214.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.93

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017781436).
• BP6: Variant 2-98655513-T-C is Benign according to our data. Variant chr2-98655513-T-C is described in ClinVar as [Benign]. Clinvar id is 710312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT4A	NM_012214.3	c.706A>G	p.Thr236Ala	missense_variant	8/16	ENST00000393487.6
MGAT4A	NM_001160154.2	c.322A>G	p.Thr108Ala	missense_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT4A	ENST00000393487.6	c.706A>G	p.Thr236Ala	missense_variant	8/16	5	NM_012214.3	P1

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1046 AN: 152204 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00651 AC: 1611 AN: 247536 Hom.: 7 AF XY: 0.00683 AC XY: 914 AN XY: 133828

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00455

Gnomad FIN exome AF: 0.00570

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00780

GnomAD4 exome AF: 0.00993 AC: 14455 AN: 1455852 Hom.: 93 Cov.: 28 AF XY: 0.00967 AC XY: 7009 AN XY: 724460

Gnomad4 AFR exome AF: 0.00165

Gnomad4 AMR exome AF: 0.00378

Gnomad4 ASJ exome AF: 0.000576

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00509

Gnomad4 FIN exome AF: 0.00647

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.00964

GnomAD4 genome AF: 0.00687 AC: 1046 AN: 152322 Hom.: 4 Cov.: 32 AF XY: 0.00666 AC XY: 496 AN XY: 74488

Gnomad4 AFR AF: 0.00216

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00929 Hom.: 11

Bravo AF: 0.00656

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.0107 AC: 92

ExAC AF: 0.00676 AC: 821

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.27
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;.;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
MetaRNN	Benign	0.018	T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.4	M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.052	T;T;D;T
Sift4G	Uncertain	0.053	T;T;T;T
Polyphen		1.0	D;D;.;D
Vest4		0.79
MVP		0.78
MPC		0.46
ClinPred		0.043	T
GERP RS		5.1
Varity_R		0.40
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs61748145; hg19: chr2-99271976;