NM_001478.5:c.754C>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001478.5(B4GALNT1):c.754C>A(p.Arg252Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,447,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R252H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

B4GALNT1
NM_001478.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

Publications

2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

B4GALNT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2442264).

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	UniProt
B4GALNT1	NM_001478.5	MANE Select	c.754C>A	p.Arg252Ser	missense	Exon 7 of 11	NP_001469.1	Q00973-1
B4GALNT1	NM_001413967.1		c.754C>A	p.Arg252Ser	missense	Exon 7 of 11	NP_001400896.1
B4GALNT1	NM_001413968.1		c.754C>A	p.Arg252Ser	missense	Exon 7 of 11	NP_001400897.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.754C>A	p.Arg252Ser	missense	Exon 7 of 11	ENSP00000341562.4	Q00973-1
B4GALNT1	ENST00000882412.1		c.754C>A	p.Arg252Ser	missense	Exon 7 of 11	ENSP00000552471.1
B4GALNT1	ENST00000954202.1		c.754C>A	p.Arg252Ser	missense	Exon 6 of 10	ENSP00000624261.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246612

AF XY:

0.00000751

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447144

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33174

American (AMR)

AF:

0.00

AC:

AN:

43870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25780

East Asian (EAS)

AF:

0.00

AC:

AN:

39344

South Asian (SAS)

AF:

0.00

AC:

AN:

85176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1101184

Other (OTH)

AF:

0.00

AC:

AN:

59710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.35

Eigen

Benign

-0.060

Eigen_PC

Benign

0.068

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0055

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

3.8

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.60

REVEL

Benign

0.040

Sift

Benign

0.57

Sift4G

Benign

0.63

Polyphen

0.65

Vest4

0.52

MutPred

0.42

Gain of catalytic residue at P256 (P = 0)

MVP

0.28

MPC

0.27

ClinPred

0.57

GERP RS

4.3

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.52

gMVP

0.59

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over