Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001478.5(B4GALNT1):c.1077C>A(p.Phe359Leu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. F359F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

B4GALNT1
NM_001478.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.286

Publications

0 publications found

Variant links:

Genes affected

B4GALNT1 (HGNC:4117): (beta-1,4-N-acetyl-galactosaminyltransferase 1) GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

B4GALNT1 Gene-Disease associations (from GenCC):

complex hereditary spastic paraplegia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 26
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

B4GALNT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.826

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001478.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
B4GALNT1	NM_001478.5	MANE Select	c.1077C>A	p.Phe359Leu	missense	Exon 9 of 11	NP_001469.1
B4GALNT1	NM_001413967.1		c.1212C>A	p.Phe404Leu	missense	Exon 9 of 11	NP_001400896.1
B4GALNT1	NM_001413968.1		c.1212C>A	p.Phe404Leu	missense	Exon 9 of 11	NP_001400897.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.1077C>A	p.Phe359Leu	missense	Exon 9 of 11	ENSP00000341562.4
B4GALNT1	ENST00000418555.6	TSL:2	c.912C>A	p.Phe304Leu	missense	Exon 8 of 10	ENSP00000401601.2
B4GALNT1	ENST00000547741.1	TSL:4	c.90C>A	p.Phe30Leu	missense	Exon 2 of 4	ENSP00000448577.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.38

MutationAssessor

Pathogenic

3.2

PhyloP100

0.29

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.51

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.76

MutPred

0.77

Gain of catalytic residue at V360 (P = 0.0382)

MVP

0.69

MPC

2.0

ClinPred

1.0

GERP RS

-1.4

Varity_R

0.73

gMVP

0.78

Mutation Taster

=62/38

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

12-57628188-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over