rs2246945

Positions:

• chr3-138124634-G-A
• chr3-138124634-G-T

Variant summary

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

The NM_016161.3(A4GNT):​c.653C>T​(p.Ala218Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A218D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: A4GNT NM_016161.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

Genes affected

A4GNT (HGNC:17968): (alpha-1,4-N-acetylglucosaminyltransferase) This gene encodes a protein from the glycosyltransferase 32 family. The enzyme catalyzes the transfer of N-acetylglucosamine (GlcNAc) to core 2 branched O-glycans. It forms a unique glycan, GlcNAcalpha1-->4Galbeta-->R and is largely associated with the Golgi apparatus membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04304716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A4GNT	NM_016161.3	c.653C>T	p.Ala218Val	missense_variant	3/3	ENST00000236709.4	NP_057245.1
A4GNT	XM_017006543.3	c.653C>T	p.Ala218Val	missense_variant	3/3		XP_016862032.1
A4GNT	XM_017006544.2	c.653C>T	p.Ala218Val	missense_variant	3/3		XP_016862033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A4GNT	ENST00000236709.4	c.653C>T	p.Ala218Val	missense_variant	3/3	1	NM_016161.3	ENSP00000236709.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.8
DANN	Benign	0.87
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.21
Sift	Benign	0.10	T
Sift4G	Benign	0.28	T
Polyphen		0.0060	B
Vest4		0.075
MutPred		0.47		Gain of sheet (P = 0.0043);
MVP		0.22
MPC		0.13
ClinPred		0.093	T
GERP RS		-1.8
Varity_R		0.078
gMVP		0.40

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: rs2246945; hg19: chr3-137843476;