chr14-87986637-C-A

Variant names:

• chr14-87986637-C-A
• rs77466023
• NM_000153.4:c.329-35G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000153.4(GALC):​c.329-35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000859 in 1,163,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 11 publications found

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]

GALC Gene-Disease associations (from GenCC):

• Krabbe disease

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Myriad Women’s Health, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4	c.329-35G>T		intron_variant	Intron 3 of 16	ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7	c.329-35G>T		intron_variant	Intron 3 of 16	1	NM_000153.4	ENSP00000261304.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.59e-7 AC: 1 AN: 1163868 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 593054

African (AFR) AF: 0.00 AC: 0 AN: 27382

American (AMR) AF: 0.00 AC: 0 AN: 43558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24250

East Asian (EAS) AF: 0.00 AC: 0 AN: 38312

South Asian (SAS) AF: 0.00 AC: 0 AN: 79632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5166

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842428

Other (OTH) AF: 0.00 AC: 0 AN: 50532

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.3
DANN	Benign	0.57
PhyloP100		0.13

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

Other links and lift over

dbSNP: rs77466023; hg19: chr14-88452981;