16-67149729-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033309.3(B3GNT9):c.757C>A(p.Leu253Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: B3GNT9 NM_033309.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

Genes affected

B3GNT9 (HGNC:28714): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 9) Predicted to enable UDP-glycosyltransferase activity. Predicted to be involved in poly-N-acetyllactosamine biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28113884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GNT9	NM_033309.3	c.757C>A	p.Leu253Ile	missense_variant	2/2	ENST00000449549.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GNT9	ENST00000449549.4	c.757C>A	p.Leu253Ile	missense_variant	2/2	1	NM_033309.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246160 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 0.00000205 AC: 3 AN: 1461312 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000827 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.757C>A (p.L253I) alteration is located in exon 2 (coding exon 1) of the B3GNT9 gene. This alteration results from a C to A substitution at nucleotide position 757, causing the leucine (L) at amino acid position 253 to be replaced by an isoleucine (I). 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	0.28
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.49
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0098	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N
MutationTaster	Benign	0.93	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.15
Sift	Benign	0.065	T
Sift4G	Benign	0.066	T
Polyphen		0.88	P
Vest4		0.24
MutPred		0.53		Gain of sheet (P = 0.1451);
MVP		0.46
MPC		1.8
ClinPred		0.64	D
GERP RS		3.0
Varity_R		0.067
gMVP		0.51

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: rs756339187; hg19: chr16-67183632;