14-87950751-GAA-GAAA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_000153.4(GALC):c.1162-4_1162-3insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: GALC NM_000153.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.150

Genes affected

GALC (HGNC:4115): (galactosylceramidase) This gene encodes a lysosomal protein which hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations in this gene have been associated with Krabbe disease, also known as globoid cell leukodystrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP6: Variant 14-87950751-G-GA is Benign according to our data. Variant chr14-87950751-G-GA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 314750.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALC	NM_000153.4	c.1162-4_1162-3insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261304.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALC	ENST00000261304.7	c.1162-4_1162-3insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000153.4	P1

Frequencies

GnomAD3 genomes AF: 0.000241 AC: 36 AN: 149428 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000861

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000486

GnomAD4 exome AF: 0.0000344 AC: 39 AN: 1134522 Hom.: 0 Cov.: 0 AF XY: 0.0000350 AC XY: 20 AN XY: 571880

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000107

Gnomad4 OTH exome AF: 0.0000210

GnomAD4 genome AF: 0.000241 AC: 36 AN: 149540 Hom.: 0 Cov.: 0 AF XY: 0.000192 AC XY: 14 AN XY: 72838

Gnomad4 AFR AF: 0.000859

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000481

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency Uncertain:1 Benign:1

Benign, criteria provided, single submitter	clinical testing	Invitae	Oct 18, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs11300320; hg19: chr14-88417095;