11-77039985-G-C

Variant names:

• chr11-77039985-G-C
• rs1555027531
• NM_138706.5:c.434G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138706.5(B3GNT6):​c.434G>C​(p.Ser145Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,426,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: B3GNT6 NM_138706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.03

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05021271).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT6	NM_138706.5	c.434G>C	p.Ser145Thr	missense_variant	Exon 2 of 2	ENST00000622824.1	NP_619651.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GNT6	ENST00000622824.1	c.434G>C	p.Ser145Thr	missense_variant	Exon 2 of 2	1	NM_138706.5	ENSP00000484640.1
B3GNT6	ENST00000528622.5	c.*70G>C		downstream_gene_variant		3		ENSP00000435628.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000526 AC: 1 AN: 190246 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 106984

Gnomad AFR exome AF: 0.000105

Gnomad AMR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000491 AC: 7 AN: 1426242 Hom.: 0 Cov.: 30 AF XY: 0.00000282 AC XY: 2 AN XY: 708704

Gnomad4 AFR exome AF: 0.0000312

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: 0.0000273

Gnomad4 NFE exome AF: 0.00000453

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.434G>C (p.S145T) alteration is located in exon 2 (coding exon 1) of the B3GNT6 gene. This alteration results from a G to C substitution at nucleotide position 434, causing the serine (S) at amino acid position 145 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.64
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.061	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Pathogenic	0.84	D
Sift4G	Benign	0.64	T
Polyphen		0.13	B
Vest4		0.065
MutPred		0.29		Gain of phosphorylation at S145 (P = 0.079);
MVP		0.15
ClinPred		0.034	T
GERP RS		2.4
Varity_R		0.078
gMVP		0.34

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: rs1555027531; hg19: chr11-76751029;