rs34752717

Positions:

• chr14-87941372-TAA-T
• chr14-87941372-TAA-TA
• chr14-87941372-TAA-TAAA
• chr14-87941372-TAA-TAAAA
• chr14-87941372-TAA-TAAAAA
• chr14-87941372-TAA-TAAAAAA
• chr14-87941372-TAA-TAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_000153.4(GALC):​c.1834+21_1834+22del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,273,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 14-87941372-TAA-T is Benign according to our data. Variant chr14-87941372-TAA-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALC	NM_000153.4	c.1834+21_1834+22del		intron_variant		ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7	c.1834+21_1834+22del		intron_variant		1	NM_000153.4	ENSP00000261304	P1

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 146946 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000678

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000284 AC: 320 AN: 1126366 Hom.: 0 AF XY: 0.000252 AC XY: 144 AN XY: 570984

Gnomad4 AFR exome AF: 0.000553

Gnomad4 AMR exome AF: 0.0000807

Gnomad4 ASJ exome AF: 0.000318

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000109

Gnomad4 FIN exome AF: 0.000234

Gnomad4 NFE exome AF: 0.000324

Gnomad4 OTH exome AF: 0.000125

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 146946 Hom.: 0 Cov.: 0 AF XY: 0.0000281 AC XY: 2 AN XY: 71246

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000678

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00114 Hom.: 978

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs34752717; hg19: chr14-88407716;