rs782676328

Variant names:

• chr11-77040005-C-T
• rs782676328
• NM_138706.5:c.454C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_138706.5(B3GNT6):​c.454C>T​(p.Arg152Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,422,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R152H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: B3GNT6 NM_138706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15
• Publications: 2 publications found

Genes affected

B3GNT6 (HGNC:24141): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6) The protein encoded by this gene is a beta-1,3-N-acetylglucosaminyltransferase that adds an N-acetylglucosamine moiety to N-acetylgalactosamine-modified serine or threonine. The encoded enzyme is responsible for creating the core 3 structure of O-glycans, which are important components of mucin-type glycoproteins. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Trascript score misZ: -2.0224 (below the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138706.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT6	NM_138706.5	MANE Select	c.454C>T	p.Arg152Cys	missense	Exon 2 of 2	NP_619651.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT6	ENST00000622824.1	TSL:1 MANE Select	c.454C>T	p.Arg152Cys	missense	Exon 2 of 2	ENSP00000484640.1	Q6ZMB0-1
	B3GNT6	ENST00000854987.1		c.454C>T	p.Arg152Cys	missense	Exon 2 of 2	ENSP00000525046.1
	B3GNT6	ENST00000854988.1		c.454C>T	p.Arg152Cys	missense	Exon 2 of 2	ENSP00000525047.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000548 AC: 1 AN: 182394 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000704

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1422380 Hom.: 0 Cov.: 30 AF XY: 0.00000283 AC XY: 2 AN XY: 706460

African (AFR) AF: 0.00 AC: 0 AN: 31964

American (AMR) AF: 0.00 AC: 0 AN: 41564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25474

East Asian (EAS) AF: 0.000106 AC: 4 AN: 37874

South Asian (SAS) AF: 0.00 AC: 0 AN: 83496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101162

Other (OTH) AF: 0.00 AC: 0 AN: 59172

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000880 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.084
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		1.1
PrimateAI	Pathogenic	0.94	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.75	P
Vest4		0.61
MutPred		0.65		Loss of MoRF binding (P = 0.0143)
MVP		0.33
ClinPred		0.73	D
GERP RS		1.4
Varity_R		0.22
gMVP		0.70
Mutation Taster		=91/9	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

Other links and lift over

dbSNP: rs782676328; hg19: chr11-76751049; COSMIC: COSV100845758; COSMIC: COSV100845758;