chr12-122206899-G-T

Position:

• chr12-122206899-G-T

Variant summary

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

The NM_030765.4(B3GNT4):​c.648G>T​(p.Lys216Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GNT4 NM_030765.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.416

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]

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=0.27767098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GNT4	NM_030765.4	c.648G>T	p.Lys216Asn	missense_variant	3/3	ENST00000324189.5	NP_110392.1
B3GNT4	NM_001330492.2	c.573G>T	p.Lys191Asn	missense_variant	2/2		NP_001317421.1
B3GNT4	XM_047429535.1	c.573G>T	p.Lys191Asn	missense_variant	2/2		XP_047285491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GNT4	ENST00000324189.5	c.648G>T	p.Lys216Asn	missense_variant	3/3	1	NM_030765.4	ENSP00000319636	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Jun 22, 2023

The c.648G>T (p.K216N) alteration is located in exon 3 (coding exon 2) of the B3GNT4 gene. This alteration results from a G to T substitution at nucleotide position 648, causing the lysine (K) at amino acid position 216 to be replaced by an asparagine (N). 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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T;.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.15
Sift	Benign	0.069	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.28	B;.;.
Vest4		0.38
MutPred		0.67		Loss of ubiquitination at K216 (P = 0.0255);.;.;
MVP		0.56
MPC		0.024
ClinPred		0.93	D
GERP RS		0.069
Varity_R		0.42
gMVP		0.78

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: rs377393964; hg19: chr12-122691446;