16-67149566-G-A

Position:

• chr16-67149566-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033309.3(B3GNT9):​c.920C>T​(p.Ala307Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: B3GNT9 NM_033309.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12370774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GNT9	NM_033309.3	c.920C>T	p.Ala307Val	missense_variant	2/2	ENST00000449549.4	NP_171608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GNT9	ENST00000449549.4	c.920C>T	p.Ala307Val	missense_variant	2/2	1	NM_033309.3	ENSP00000400157.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722712

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000830 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

May 20, 2024

The c.920C>T (p.A307V) alteration is located in exon 2 (coding exon 1) of the B3GNT9 gene. This alteration results from a C to T substitution at nucleotide position 920, causing the alanine (A) at amino acid position 307 to be replaced by a valine (V). 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	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.032
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.057	T
Polyphen		0.66	P
Vest4		0.13
MutPred		0.34		Loss of helix (P = 0.2022);
MVP		0.44
MPC		1.0
ClinPred		0.45	T
GERP RS		2.9
Varity_R		0.056
gMVP		0.39

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: rs761432548; hg19: chr16-67183469; COSMIC: COSV99531680; COSMIC: COSV99531680;