chr12-122206427-C-T

Position:

• chr12-122206427-C-T

Variant summary

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

The NM_030765.4(B3GNT4):​c.176C>T​(p.Pro59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GNT4 NM_030765.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.337

Genes affected

B3GNT4 (HGNC:15683): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase protein family. The encoded enzyme is involved in the biosynthesis of poly-N-acetyllactosamine chains and prefers lacto-N-neotetraose as a substrate. It is a type II transmembrane protein. [provided by RefSeq, Jul 2008]

B3GNT4 (HGNC:):

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=0.060550958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GNT4	NM_030765.4	c.176C>T	p.Pro59Leu	missense_variant	3/3	ENST00000324189.5	NP_110392.1
B3GNT4	NM_001330492.2	c.101C>T	p.Pro34Leu	missense_variant	2/2		NP_001317421.1
B3GNT4	XM_047429535.1	c.101C>T	p.Pro34Leu	missense_variant	2/2		XP_047285491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GNT4	ENST00000324189.5	c.176C>T	p.Pro59Leu	missense_variant	3/3	1	NM_030765.4	ENSP00000319636.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Dec 06, 2024

The c.176C>T (p.P59L) alteration is located in exon 3 (coding exon 2) of the B3GNT4 gene. This alteration results from a C to T substitution at nucleotide position 176, causing the proline (P) at amino acid position 59 to be replaced by a leucine (L). 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	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.8
DANN	Benign	0.62
DEOGEN2	Benign	0.031	T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.45	T;.;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.44	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.11
MutPred		0.32		Loss of disorder (P = 0.0217);.;.;
MVP		0.34
MPC		0.011
ClinPred		0.058	T
GERP RS		3.2
Varity_R		0.025
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-122690974;