19-17811986-G-A

Variant names:

• chr19-17811986-G-A
• rs36686
• NM_014256.4:c.983G>A

Variant summary

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

The NM_014256.4(B3GNT3):​c.983G>A​(p.Arg328His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,603,612 control chromosomes in the GnomAD database, including 468,645 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.79 (48333 hom., cov: 32)
  • Exomes 𝑓: 0.76 (420312 hom.)
• Consequence: B3GNT3 NM_014256.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 37 publications found

Genes affected

B3GNT3 (HGNC:13528): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein and contains a signal anchor that is not cleaved. It prefers the substrates of lacto-N-tetraose and lacto-N-neotetraose, and is involved in the biosynthesis of poly-N-acetyllactosamine chains and the biosynthesis of the backbone structure of dimeric sialyl Lewis a. It plays dominant roles in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.214042E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT3	NM_014256.4	c.983G>A	p.Arg328His	missense_variant	Exon 3 of 3	ENST00000318683.7	NP_055071.2
B3GNT3	XM_011527626.3	c.983G>A	p.Arg328His	missense_variant	Exon 3 of 3		XP_011525928.1
B3GNT3	XM_047438042.1	c.983G>A	p.Arg328His	missense_variant	Exon 3 of 3		XP_047293998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GNT3	ENST00000318683.7	c.983G>A	p.Arg328His	missense_variant	Exon 3 of 3	1	NM_014256.4	ENSP00000321874.5
B3GNT3	ENST00000595387.1	c.983G>A	p.Arg328His	missense_variant	Exon 3 of 3	1		ENSP00000472638.1
B3GNT3	ENST00000599265.5	c.*233G>A		downstream_gene_variant		3		ENSP00000471733.1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120579 AN: 152104 Hom.: 48294 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.774

GnomAD2 exomes AF: 0.761 AC: 185707 AN: 244150 AF XY: 0.757

Gnomad AFR exome AF: 0.885

Gnomad AMR exome AF: 0.807

Gnomad ASJ exome AF: 0.786

Gnomad EAS exome AF: 0.486

Gnomad FIN exome AF: 0.839

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.762

GnomAD4 exome AF: 0.759 AC: 1101909 AN: 1451390 Hom.: 420312 Cov.: 92 AF XY: 0.758 AC XY: 547377 AN XY: 722418

African (AFR) AF: 0.885 AC: 29621 AN: 33474

American (AMR) AF: 0.805 AC: 36011 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 20488 AN: 26136

East Asian (EAS) AF: 0.520 AC: 20653 AN: 39700

South Asian (SAS) AF: 0.737 AC: 63565 AN: 86258

European-Finnish (FIN) AF: 0.835 AC: 35962 AN: 43044

Middle Eastern (MID) AF: 0.796 AC: 4590 AN: 5766

European-Non Finnish (NFE) AF: 0.760 AC: 844942 AN: 1111948

Other (OTH) AF: 0.764 AC: 46077 AN: 60342

GnomAD4 genome AF: 0.793 AC: 120673 AN: 152222 Hom.: 48333 Cov.: 32 AF XY: 0.794 AC XY: 59089 AN XY: 74422

African (AFR) AF: 0.877 AC: 36472 AN: 41568

American (AMR) AF: 0.803 AC: 12273 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3472

East Asian (EAS) AF: 0.509 AC: 2624 AN: 5158

South Asian (SAS) AF: 0.712 AC: 3437 AN: 4824

European-Finnish (FIN) AF: 0.840 AC: 8913 AN: 10612

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51860 AN: 67992

Other (OTH) AF: 0.768 AC: 1618 AN: 2108

Alfa AF: 0.767 Hom.: 155096

Bravo AF: 0.791

TwinsUK AF: 0.774 AC: 2869

ALSPAC AF: 0.763 AC: 2939

ESP6500AA AF: 0.877 AC: 3865

ESP6500EA AF: 0.755 AC: 6493

ExAC AF: 0.763 AC: 92625

Asia WGS AF: 0.648 AC: 2255 AN: 3478

EpiCase AF: 0.754

EpiControl AF: 0.760

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.8
DANN	Benign	0.96
DEOGEN2	Benign	0.064	T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.24	.;T
MetaRNN	Benign	0.0000012	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		-0.36
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.024
Sift	Benign	0.26	T;.
Sift4G	Uncertain	0.017	D;D
Polyphen		0.45	B;B
Vest4		0.020
MPC		0.85
ClinPred		0.0024	T
GERP RS		3.1
Varity_R		0.032
gMVP		0.60
Mutation Taster		=99/1	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: rs36686; hg19: chr19-17922795; COSMIC: COSV57952753; COSMIC: COSV57952753;