3-161090059-A-T

Position:

• chr3-161090059-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001349162.2(B3GALNT1):​c.211T>A​(p.Cys71Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 166,850 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.027 (204 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (3 hom.)
• Consequence: B3GALNT1 NM_001349162.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.368

Genes affected

B3GALNT1 (HGNC:918): (beta-1,3-N-acetylgalactosaminyltransferase 1 (Globoside blood group)) This gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). The encoded protein of this gene does not use N-acetylglucosamine as an acceptor sugar at all. [provided by RefSeq, Mar 2017]

B3GALNT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017833412).
• BP6: Variant 3-161090059-A-T is Benign according to our data. Variant chr3-161090059-A-T is described in ClinVar as [Benign]. Clinvar id is 3038134.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALNT1	NM_003781.4	c.-34-3271T>A		intron_variant		ENST00000320474.10	NP_003772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALNT1	ENST00000320474.10	c.-34-3271T>A		intron_variant		1	NM_003781.4	ENSP00000323479.4

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4149 AN: 152190 Hom.: 203 Cov.: 33

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00413 AC: 27 AN: 6542 Hom.: 3 AF XY: 0.00185 AC XY: 7 AN XY: 3788

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.00364

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000694

Gnomad OTH exome AF: 0.00549

GnomAD4 exome AF: 0.00474 AC: 69 AN: 14542 Hom.: 3 Cov.: 0 AF XY: 0.00264 AC XY: 23 AN XY: 8728

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.00670

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: 0.000175

Gnomad4 OTH exome AF: 0.00906

GnomAD4 genome AF: 0.0273 AC: 4158 AN: 152308 Hom.: 204 Cov.: 33 AF XY: 0.0261 AC XY: 1944 AN XY: 74484

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0153 Hom.: 12

Bravo AF: 0.0316

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00134 AC: 18

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

B3GALNT1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.2
DANN	Benign	0.28
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0029	N
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.021
Sift	Benign	0.27	T
MutPred		0.51		Gain of relative solvent accessibility (P = 0.005);
MVP		0.16
ClinPred		0.0037	T
GERP RS		0.16

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: rs34184112; hg19: chr3-160807847;