rs11300320

chr14-87950751-GAA-Gchr14-87950751-GAA-GAchr14-87950751-GAA-GAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000153.4(GALC):c.1162-5_1162-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000752 in 1,277,986 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00085 (0 hom.)
• Consequence: GALC NM_000153.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.817

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 14-87950751-GAA-G is Benign according to our data. Variant chr14-87950751-GAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 752088.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALC	NM_000153.4	c.1162-5_1162-4del		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.1162-5_1162-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000153.4	P1

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149412 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000246

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: 0.00

GnomAD4 exome AF: 0.000851 AC: 960 AN: 1128574 Hom.: 0 AF XY: 0.000845 AC XY: 481 AN XY: 568936

Gnomad4 AFR exome AF: 0.000584

Gnomad4 AMR exome AF: 0.000471

Gnomad4 ASJ exome AF: 0.000369

Gnomad4 EAS exome AF: 0.000266

Gnomad4 SAS exome AF: 0.000902

Gnomad4 FIN exome AF: 0.000189

Gnomad4 NFE exome AF: 0.000954

Gnomad4 OTH exome AF: 0.000780

GnomAD4 genome AF: 0.00000669 AC: 1 AN: 149412 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72702

Gnomad4 AFR AF: 0.0000246

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: 0.00

Alfa AF: 0.00398 Hom.: 6173

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 25, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;