3-138124634-G-T

Variant names:

• chr3-138124634-G-T
• rs2246945
• NM_016161.3:c.653C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016161.3(A4GNT):​c.653C>A​(p.Ala218Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 1,613,930 control chromosomes in the GnomAD database, including 365,185 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.66 (33420 hom., cov: 33)
  • Exomes 𝑓: 0.67 (331765 hom.)
• Consequence: A4GNT NM_016161.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3401583E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
A4GNT	NM_016161.3	c.653C>A	p.Ala218Asp	missense_variant	Exon 3 of 3	ENST00000236709.4	NP_057245.1
A4GNT	XM_017006543.3	c.653C>A	p.Ala218Asp	missense_variant	Exon 3 of 3		XP_016862032.1
A4GNT	XM_017006544.2	c.653C>A	p.Ala218Asp	missense_variant	Exon 3 of 3		XP_016862033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
A4GNT	ENST00000236709.4	c.653C>A	p.Ala218Asp	missense_variant	Exon 3 of 3	1	NM_016161.3	ENSP00000236709.3

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100730 AN: 151952 Hom.: 33389 Cov.: 33

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.677

GnomAD2 exomes AF: 0.654 AC: 164344 AN: 251294 AF XY: 0.656

Gnomad AFR exome AF: 0.645

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.670

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.668

Gnomad OTH exome AF: 0.662

GnomAD4 exome AF: 0.673 AC: 983924 AN: 1461860 Hom.: 331765 Cov.: 83 AF XY: 0.672 AC XY: 488644 AN XY: 727230

African (AFR) AF: 0.649 AC: 21731 AN: 33480

American (AMR) AF: 0.642 AC: 28728 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 17607 AN: 26136

East Asian (EAS) AF: 0.630 AC: 24997 AN: 39700

South Asian (SAS) AF: 0.630 AC: 54344 AN: 86258

European-Finnish (FIN) AF: 0.639 AC: 34149 AN: 53416

Middle Eastern (MID) AF: 0.623 AC: 3595 AN: 5768

European-Non Finnish (NFE) AF: 0.682 AC: 758282 AN: 1111984

Other (OTH) AF: 0.670 AC: 40491 AN: 60394

GnomAD4 genome AF: 0.663 AC: 100810 AN: 152070 Hom.: 33420 Cov.: 33 AF XY: 0.663 AC XY: 49254 AN XY: 74330

African (AFR) AF: 0.653 AC: 27075 AN: 41486

American (AMR) AF: 0.703 AC: 10738 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3470

East Asian (EAS) AF: 0.653 AC: 3379 AN: 5178

South Asian (SAS) AF: 0.632 AC: 3043 AN: 4812

European-Finnish (FIN) AF: 0.634 AC: 6693 AN: 10558

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.669 AC: 45476 AN: 67978

Other (OTH) AF: 0.671 AC: 1414 AN: 2108

Alfa AF: 0.668 Hom.: 47621

Bravo AF: 0.667

TwinsUK AF: 0.689 AC: 2553

ALSPAC AF: 0.678 AC: 2614

ESP6500AA AF: 0.643 AC: 2835

ESP6500EA AF: 0.669 AC: 5756

ExAC AF: 0.652 AC: 79171

Asia WGS AF: 0.607 AC: 2114 AN: 3478

EpiCase AF: 0.668

EpiControl AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.12
DANN	Benign	0.26
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.015	T
MetaRNN	Benign	0.0000023	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.28	N
PhyloP100		-0.35
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.16
Sift	Benign	0.91	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.16
ClinPred		0.0067	T
GERP RS		-1.8
Varity_R		0.091
gMVP		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2246945; hg19: chr3-137843476; COSMIC: COSV52628404;