rs190148089

Variant names:

• chr3-161104335-A-C
• rs190148089
• NM_003781.4:c.-237T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_003781.4(B3GALNT1):​c.-237T>G variant causes a 5 prime UTR premature start codon gain 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: B3GALNT1 NM_003781.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign no assertion criteria provided 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

Our verdict: Benign. The variant received -9 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 no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALNT1	NM_003781.4	c.-237T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	ENST00000320474.10	NP_003772.1
B3GALNT1	NM_003781.4	c.-237T>G		5_prime_UTR_variant	Exon 2 of 5	ENST00000320474.10	NP_003772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALNT1	ENST00000320474.10	c.-237T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	1	NM_003781.4	ENSP00000323479.4
B3GALNT1	ENST00000320474.10	c.-237T>G		5_prime_UTR_variant	Exon 2 of 5	1	NM_003781.4	ENSP00000323479.4

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

GnomAD2 exomes AF: 0.00131 AC: 179 AN: 136878 AF XY: 0.00108

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 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

African (AFR) AF: 0.000205 AC: 5 AN: 24410

American (AMR) AF: 0.00198 AC: 56 AN: 28252

Ashkenazi Jewish (ASJ) AF: 0.00232 AC: 37 AN: 15940

East Asian (EAS) AF: 0.00 AC: 0 AN: 12840

South Asian (SAS) AF: 0.0000525 AC: 4 AN: 76190

European-Finnish (FIN) AF: 0.000995 AC: 13 AN: 13066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4402

European-Non Finnish (NFE) AF: 0.00162 AC: 1494 AN: 920820

Other (OTH) AF: 0.00157 AC: 65 AN: 41526

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

African (AFR) AF: 0.000192 AC: 8 AN: 41570

American (AMR) AF: 0.00333 AC: 51 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00163 AC: 111 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

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: no assertion criteria provided

Submissions by phenotype

B3GALNT1-related disorder Benign:1

Jan 31, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		-0.36
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
PromoterAI		0.033	Neutral
Mutation Taster		=299/1	polymorphism

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

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Other links and lift over

dbSNP: rs190148089; hg19: chr3-160822123;