3-119224170-C-T

Position:

• chr3-119224170-C-T

Variant summary

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

The NM_003778.4(B4GALT4):​c.562G>A​(p.Asp188Asn) variant causes a missense change. 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: B4GALT4 NM_003778.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86

Genes affected

B4GALT4 (HGNC:927): (beta-1,4-galactosyltransferase 4) This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. The enzyme encoded by this gene appears to mainly play a role in glycolipid biosynthesis. Two alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

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
B4GALT4	NM_003778.4	c.562G>A	p.Asp188Asn	missense_variant	5/8	ENST00000393765.7	NP_003769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALT4	ENST00000393765.7	c.562G>A	p.Asp188Asn	missense_variant	5/8	1	NM_003778.4	ENSP00000377360	P1

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

Oct 02, 2023

The c.562G>A (p.D188N) alteration is located in exon 6 (coding exon 3) of the B4GALT4 gene. This alteration results from a G to A substitution at nucleotide position 562, causing the aspartic acid (D) at amino acid position 188 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	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.082	T;T;T;T
Eigen	Benign	0.074
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.6	M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.19
Sift	Benign	0.16	T;T;T;T
Sift4G	Benign	0.085	T;T;T;T
Polyphen		0.23	B;.;B;B
Vest4		0.66
MutPred		0.64		Loss of ubiquitination at K183 (P = 0.0699);Loss of ubiquitination at K183 (P = 0.0699);Loss of ubiquitination at K183 (P = 0.0699);Loss of ubiquitination at K183 (P = 0.0699);
MVP		0.50
MPC		1.4
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.37
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-118943017;