3-161104335-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_003781.4(B3GALNT1):c.-237T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,289,766 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: B3GALNT1 NM_003781.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.359

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004692793).
• BP6: Variant 3-161104335-A-C is Benign according to our data. Variant chr3-161104335-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3035261.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALNT1	NM_003781.4	c.-237T>G		5_prime_UTR_variant	2/5	ENST00000320474.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALNT1	ENST00000320474.10	c.-237T>G		5_prime_UTR_variant	2/5	1	NM_003781.4	P1

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 186 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00131 AC: 179 AN: 136878 Hom.: 0 AF XY: 0.00108 AC XY: 80 AN XY: 74324

Gnomad AFR exome AF: 0.000311

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00301

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000445

Gnomad FIN exome AF: 0.000557

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.00147 AC: 1674 AN: 1137446 Hom.: 3 Cov.: 30 AF XY: 0.00144 AC XY: 801 AN XY: 558012

Gnomad4 AFR exome AF: 0.000205

Gnomad4 AMR exome AF: 0.00198

Gnomad4 ASJ exome AF: 0.00232

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000525

Gnomad4 FIN exome AF: 0.000995

Gnomad4 NFE exome AF: 0.00162

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00122 AC: 186 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74476

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00161 Hom.: 0

Bravo AF: 0.00131

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00104 AC: 4

ExAC AF: 0.000735 AC: 12

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

B3GALNT1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 31, 2022

This variant is classified as likely 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	-0.46	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	8.9
Dann	Benign	0.68
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.079	N
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PROVEAN	Benign	0.090	N
REVEL	Benign	0.051
Sift	Pathogenic	0.0	D
MVP		0.30
ClinPred		0.014	T
GERP RS		1.1

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: rs190148089; hg19: chr3-160822123;