NM_001478.5:c.1114_1119delGACGTG

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PM4PP3

The NM_001478.5(B4GALNT1):​c.1114_1119delGACGTG​(p.Asp372_Val373del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

B4GALNT1
NM_001478.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.79

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001478.5.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
B4GALNT1NM_001478.5 linkc.1114_1119delGACGTG p.Asp372_Val373del conservative_inframe_deletion Exon 9 of 11 ENST00000341156.9 NP_001469.1 Q00973-1B4DSP5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
B4GALNT1ENST00000341156.9 linkc.1114_1119delGACGTG p.Asp372_Val373del conservative_inframe_deletion Exon 9 of 11 1 NM_001478.5 ENSP00000341562.4 Q00973-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
250976
AF XY:
0.00
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461686
Hom.:
0
AF XY:
0.00000138
AC XY:
1
AN XY:
727170
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53230
Middle Eastern (MID)
AF:
0.000347
AC:
2
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112000
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.000111
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Spastic paraplegia Uncertain:1
Jun 26, 2020
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant, c.1114_1119del, results in the deletion of 2 amino acid(s) of the B4GALNT1 protein (p.Asp372_Val373del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of hereditary spastic paraplegia (Invitae). ClinVar contains an entry for this variant (Variation ID: 458219). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
8.8

Splicing

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

Publications

Other links and lift over

dbSNP: rs771698791; hg19: chr12-58021928; API