NM_001478.5:c.514G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001478.5(B4GALNT1):c.514G>C(p.Gly172Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,609,128 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G172S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.028 ( 84 hom., cov: 33)

Exomes 𝑓: 0.018 ( 313 hom. )

Consequence

B4GALNT1
NM_001478.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.526

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021012425).

BP6

Variant 12-57630495-C-G is Benign according to our data. Variant chr12-57630495-C-G is described in ClinVar as Benign. ClinVar VariationId is 380791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0279 (4244/152302) while in subpopulation AFR AF = 0.0485 (2014/41554). AF 95% confidence interval is 0.0467. There are 84 homozygotes in GnomAd4. There are 2156 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 84 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT1	NM_001478.5 link	c.514G>C	p.Gly172Arg	missense_variant	Exon 5 of 11	ENST00000341156.9	NP_001469.1	Q00973-1B4DSP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156.9 link	c.514G>C	p.Gly172Arg	missense_variant	Exon 5 of 11	1	NM_001478.5	ENSP00000341562.4		Q00973-1

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4241

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0503

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0215

GnomAD2 exomes

AF:

0.0191

AC:

4719

AN:

246592

AF XY:

0.0188

show subpopulations

Gnomad AFR exome

AF:

0.0461

Gnomad AMR exome

AF:

0.00637

Gnomad ASJ exome

AF:

0.0247

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0461

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.0183

AC:

26593

AN:

1456826

Hom.:

313

Cov.:

AF XY:

0.0182

AC XY:

13168

AN XY:

724394

show subpopulations

African (AFR)

AF:

0.0490

AC:

1630

AN:

33284

American (AMR)

AF:

0.00751

AC:

330

AN:

43966

Ashkenazi Jewish (ASJ)

AF:

0.0234

AC:

602

AN:

25746

East Asian (EAS)

AF:

0.000126

AC:

AN:

39660

South Asian (SAS)

AF:

0.0193

AC:

1651

AN:

85398

European-Finnish (FIN)

AF:

0.0445

AC:

2370

AN:

53234

Middle Eastern (MID)

AF:

0.0318

AC:

182

AN:

5718

European-Non Finnish (NFE)

AF:

0.0168

AC:

18651

AN:

1109626

Other (OTH)

AF:

0.0195

AC:

1172

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

1401

2802

4204

5605

7006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0279

AC:

4244

AN:

152302

Hom.:

Cov.:

AF XY:

0.0290

AC XY:

2156

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0485

AC:

2014

AN:

41554

American (AMR)

AF:

0.0121

AC:

186

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0178

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0503

AC:

534

AN:

10608

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0189

AC:

1289

AN:

68024

Other (OTH)

AF:

0.0213

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

217

434

652

869

1086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0170

Hom.:

Bravo

AF:

0.0253

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0132

AC:

ESP6500AA

AF:

0.0497

AC:

219

ESP6500EA

AF:

0.0180

AC:

155

ExAC

AF:

0.0198

AC:

2399

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

May 05, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.20

T;.;T;.;.;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.86

D;D;D;.;D;D

MetaRNN

Benign

0.0021

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.;L;L;.

PhyloP100

0.53

PrimateAI

Benign

0.40

PROVEAN

Benign

0.50

N;N;.;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;T;.;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T;.

Polyphen

0.0

B;.;P;.;.;.

Vest4

0.22

MPC

0.31

ClinPred

0.014

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over