rs144922627

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001478.5(B4GALNT1):c.793G>A(p.Gly265Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,588,952 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 20 hom. )

Consequence

B4GALNT1
NM_001478.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.48

Publications

3 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: Benign. The variant received -16 ACMG points.

BP6

Variant 12-57629066-C-T is Benign according to our data. Variant chr12-57629066-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00321 (489/152310) while in subpopulation AMR AF = 0.00379 (58/15304). AF 95% confidence interval is 0.00301. There are 2 homozygotes in GnomAd4. There are 303 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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.793G>A	p.Gly265Arg	missense	Exon 7 of 11	NP_001469.1	Q00973-1
B4GALNT1	NM_001413967.1		c.793G>A	p.Gly265Arg	missense	Exon 7 of 11	NP_001400896.1
B4GALNT1	NM_001413968.1		c.793G>A	p.Gly265Arg	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.793G>A	p.Gly265Arg	missense	Exon 7 of 11	ENSP00000341562.4	Q00973-1
B4GALNT1	ENST00000882412.1		c.793G>A	p.Gly265Arg	missense	Exon 7 of 11	ENSP00000552471.1
B4GALNT1	ENST00000954202.1		c.793G>A	p.Gly265Arg	missense	Exon 6 of 10	ENSP00000624261.1

Frequencies

GnomAD3 genomes

AF:

0.00321

AC:

489

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00373

AC:

890

AN:

238488

AF XY:

0.00395

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0227

Gnomad NFE exome

AF:

0.00248

Gnomad OTH exome

AF:

0.00363

GnomAD4 exome

AF:

0.00278

AC:

3997

AN:

1436642

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

2024

AN XY:

710438

show subpopulations

African (AFR)

AF:

0.000212

AC:

AN:

32986

American (AMR)

AF:

0.00172

AC:

AN:

43112

Ashkenazi Jewish (ASJ)

AF:

0.00281

AC:

AN:

24886

East Asian (EAS)

AF:

0.00

AC:

AN:

39268

South Asian (SAS)

AF:

0.00216

AC:

180

AN:

83494

European-Finnish (FIN)

AF:

0.0209

AC:

1102

AN:

52806

Middle Eastern (MID)

AF:

0.000707

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.00219

AC:

2395

AN:

1095288

Other (OTH)

AF:

0.00279

AC:

165

AN:

59144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

209

418

627

836

1045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.00321

AC:

489

AN:

152310

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

303

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41574

American (AMR)

AF:

0.00379

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0226

AC:

240

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00226

AC:

154

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00192

Hom.:

Bravo

AF:

0.00199

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00346

AC:

420

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

B4GALNT1-related disorder (1)

Hereditary spastic paraplegia 26 (1)

not specified (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

2.5

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.080

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.96

Vest4

0.49

MutPred

0.44

Gain of catalytic residue at P263 (P = 0.001)

MVP

0.39

MPC

0.65

ClinPred

0.035

GERP RS

2.8

PromoterAI

0.029

Neutral

(source)

Varity_R

0.19

gMVP

0.80

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.28

Position offset: -1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over