6-33277613-G-A

Variant names:

• chr6-33277613-G-A
• NM_003782.4:c.194G>A

Variant summary

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

The NM_003782.4(B3GALT4):​c.194G>A​(p.Ser65Asn) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S65G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: B3GALT4 NM_003782.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.887

Genes affected

B3GALT4 (HGNC:919): (beta-1,3-galactosyltransferase 4) This gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). This gene is oriented telomere to centromere in close proximity to the ribosomal protein S18 gene. The functionality of the encoded protein is limited to ganglioseries glycolipid biosynthesis. [provided by RefSeq, Jul 2008]

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=0.03619662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALT4	NM_003782.4	c.194G>A	p.Ser65Asn	missense_variant	Exon 1 of 1	ENST00000451237.3	NP_003773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALT4	ENST00000451237.3	c.194G>A	p.Ser65Asn	missense_variant	Exon 1 of 1	6	NM_003782.4	ENSP00000390784.1

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

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.194G>A (p.S65N) alteration is located in exon 1 (coding exon 1) of the B3GALT4 gene. This alteration results from a G to A substitution at nucleotide position 194, causing the serine (S) at amino acid position 65 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	0.088
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.17	N
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.029
Sift	Benign	0.53	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.054
MutPred		0.18		Loss of glycosylation at S65 (P = 0.0054);
MVP		0.31
MPC		0.78
ClinPred		0.058	T
GERP RS		1.4
Varity_R		0.045
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr6-33245390;