chr19-17807986-C-T

Variant names:

• chr19-17807986-C-T
• rs377004909
• NM_014256.4:c.179C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014256.4(B3GNT3):​c.179C>T​(p.Pro60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,585,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.0000066 (0 hom., cov: 27)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: B3GNT3 NM_014256.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17623004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT3	NM_014256.4	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3	ENST00000318683.7	NP_055071.2
B3GNT3	XM_011527626.3	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3		XP_011525928.1
B3GNT3	XM_047438042.1	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3		XP_047293998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GNT3	ENST00000318683.7	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3	1	NM_014256.4	ENSP00000321874.5
B3GNT3	ENST00000595387.1	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3	1		ENSP00000472638.1
B3GNT3	ENST00000599265.5	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3	3		ENSP00000471733.1
B3GNT3	ENST00000600777.1	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 2	3		ENSP00000468914.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151278 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434654 Hom.: 0 Cov.: 69 AF XY: 0.00 AC XY: 0 AN XY: 714440

Gnomad4 AFR exome AF: 0.0000304

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151278 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 73878

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.9
DANN	Benign	0.82
DEOGEN2	Benign	0.053	T;T;T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.56	T;.;T;T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	.;M;.;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.8	.;D;.;.
REVEL	Benign	0.051
Sift	Benign	0.15	.;T;.;.
Sift4G	Benign	0.086	T;T;T;T
Polyphen		0.87	.;P;.;P
Vest4		0.15, 0.14
MutPred		0.25		Loss of glycosylation at P60 (P = 0.0372);Loss of glycosylation at P60 (P = 0.0372);Loss of glycosylation at P60 (P = 0.0372);Loss of glycosylation at P60 (P = 0.0372);
MVP		0.35
MPC		0.95
ClinPred		0.31	T
GERP RS		-2.0
Varity_R		0.044
gMVP		0.32

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: rs377004909; hg19: chr19-17918795; COSMIC: COSV100592868;