16-67149444-G-A

Position:

• chr16-67149444-G-A

Variant summary

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

The NM_033309.3(B3GNT9):​c.1042C>T​(p.Pro348Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: B3GNT9 NM_033309.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.80

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GNT9	NM_033309.3	c.1042C>T	p.Pro348Ser	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.1042C>T	p.Pro348Ser	missense_variant	2/2	1	NM_033309.3	ENSP00000400157.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Mar 18, 2024

The c.1042C>T (p.P348S) 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 1042, causing the proline (P) at amino acid position 348 to be replaced by a serine (S). 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	0.16
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.21
Sift	Uncertain	0.028	D
Sift4G	Benign	0.18	T
Polyphen		0.94	P
Vest4		0.57
MutPred		0.30		Gain of catalytic residue at P348 (P = 0.0513);
MVP		0.27
MPC		1.8
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.11
gMVP		0.64

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: rs1287189841; hg19: chr16-67183347;