3-138124591-C-A

Position:

• chr3-138124591-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016161.3(A4GNT):​c.696G>T​(p.Leu232Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: A4GNT NM_016161.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0730

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A4GNT	NM_016161.3	c.696G>T	p.Leu232Phe	missense_variant	3/3	ENST00000236709.4	NP_057245.1
A4GNT	XM_017006543.3	c.696G>T	p.Leu232Phe	missense_variant	3/3		XP_016862032.1
A4GNT	XM_017006544.2	c.696G>T	p.Leu232Phe	missense_variant	3/3		XP_016862033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A4GNT	ENST00000236709.4	c.696G>T	p.Leu232Phe	missense_variant	3/3	1	NM_016161.3	ENSP00000236709.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

The c.696G>T (p.L232F) alteration is located in exon 3 (coding exon 2) of the A4GNT gene. This alteration results from a G to T substitution at nucleotide position 696, causing the leucine (L) at amino acid position 232 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.0082	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.061
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.31	N
REVEL	Uncertain	0.42
Sift	Benign	0.62	T
Sift4G	Benign	0.21	T
Polyphen		0.98	D
Vest4		0.63
MutPred		0.59		Loss of catalytic residue at M228 (P = 0.0295);
MVP		0.42
MPC		0.30
ClinPred		0.70	D
GERP RS		2.4
Varity_R		0.091
gMVP		0.69

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: chr3-137843433;