3-119230002-T-G

Variant names:

• chr3-119230002-T-G
• NM_003778.4:c.98A>C

Variant summary

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

The NM_003778.4(B4GALT4):​c.98A>C​(p.Tyr33Ser) 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: 32)
• Consequence: B4GALT4 NM_003778.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

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]

B4GALT4-AS1 (HGNC:40090): (B4GALT4 antisense RNA 1)

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 rank	MANE	Protein	UniProt
B4GALT4	NM_003778.4	c.98A>C	p.Tyr33Ser	missense_variant	Exon 3 of 8	ENST00000393765.7	NP_003769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALT4	ENST00000393765.7	c.98A>C	p.Tyr33Ser	missense_variant	Exon 3 of 8	1	NM_003778.4	ENSP00000377360.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.98A>C (p.Y33S) alteration is located in exon 4 (coding exon 1) of the B4GALT4 gene. This alteration results from a A to C substitution at nucleotide position 98, causing the tyrosine (Y) at amino acid position 33 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	0.15
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.0097	T;T;T;T;T;.;T;.
Eigen	Benign	0.076
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	.;T;.;T;T;T;T;T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.;M;M;.;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;D;D
REVEL	Benign	0.28
Sift	Benign	0.18	T;T;T;T;T;T;D;D
Sift4G	Benign	0.21	T;T;T;T;.;.;.;.
Polyphen		0.98	D;.;D;D;.;.;.;.
Vest4		0.77
MutPred		0.61		Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);
MVP		0.71
MPC		1.3
ClinPred		0.69	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.82

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: chr3-118948849;