19-17811959-C-T

Position:

• chr19-17811959-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014256.4(B3GNT3):​c.956C>T​(p.Thr319Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00731 in 1,609,846 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (68 hom.)
• Consequence: B3GNT3 NM_014256.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.20

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004816413).
• BP6: Variant 19-17811959-C-T is Benign according to our data. Variant chr19-17811959-C-T is described in ClinVar as [Benign]. Clinvar id is 710761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2093/152346) while in subpopulation AFR AF= 0.0313 (1302/41572). AF 95% confidence interval is 0.0299. There are 28 homozygotes in gnomad4. There are 992 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GNT3	NM_014256.4	c.956C>T	p.Thr319Met	missense_variant	3/3	ENST00000318683.7
B3GNT3	XM_011527626.3	c.956C>T	p.Thr319Met	missense_variant	3/3
B3GNT3	XM_047438042.1	c.956C>T	p.Thr319Met	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GNT3	ENST00000318683.7	c.956C>T	p.Thr319Met	missense_variant	3/3	1	NM_014256.4	P1
B3GNT3	ENST00000595387.1	c.956C>T	p.Thr319Met	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2057 AN: 152228 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.000470

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00641

Gnomad OTH AF: 0.0162

GnomAD3 exomes AF: 0.00806 AC: 2000 AN: 248038 Hom.: 15 AF XY: 0.00783 AC XY: 1052 AN XY: 134350

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.00697

Gnomad ASJ exome AF: 0.0324

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00526

Gnomad FIN exome AF: 0.000818

Gnomad NFE exome AF: 0.00645

Gnomad OTH exome AF: 0.00720

GnomAD4 exome AF: 0.00663 AC: 9670 AN: 1457500 Hom.: 68 Cov.: 30 AF XY: 0.00662 AC XY: 4799 AN XY: 725222

Gnomad4 AFR exome AF: 0.0305

Gnomad4 AMR exome AF: 0.00698

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00566

Gnomad4 FIN exome AF: 0.00130

Gnomad4 NFE exome AF: 0.00568

Gnomad4 OTH exome AF: 0.00880

GnomAD4 genome AF: 0.0137 AC: 2093 AN: 152346 Hom.: 28 Cov.: 32 AF XY: 0.0133 AC XY: 992 AN XY: 74498

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.000470

Gnomad4 NFE AF: 0.00642

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.00930 Hom.: 20

Bravo AF: 0.0150

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.0306 AC: 135

ESP6500EA AF: 0.00907 AC: 78

ExAC AF: 0.00804 AC: 976

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.00862

EpiControl AF: 0.00936

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

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.90	D
MetaRNN	Benign	0.0048	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Benign	0.24
Sift	Benign	0.043	D;.
Sift4G	Uncertain	0.013	D;D
Polyphen		0.96	D;D
Vest4		0.15
MVP		0.55
MPC		1.3
ClinPred		0.058	T
GERP RS		4.0
Varity_R		0.12
gMVP		0.86

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: rs76106223; hg19: chr19-17922768;