14-87933931-T-A

Variant names:

• chr14-87933931-T-A
• rs114174103
• NM_000153.4:c.*801A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000153.4(GALC):​c.*801A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,451,408 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (53 hom.)
• Consequence: GALC NM_000153.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.167
• Publications: 2 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, PanelApp Australia, Genomics England PanelApp, Laboratory for Molecular Medicine, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-87933931-T-A is Benign according to our data. Variant chr14-87933931-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 314735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000153.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALC	NM_000153.4	MANE Select	c.*801A>T		3_prime_UTR	Exon 17 of 17	NP_000144.2	P54803-1
	GALC	NM_001201401.2		c.*801A>T		3_prime_UTR	Exon 16 of 16	NP_001188330.1	P54803-3
	GALC	NM_001201402.2		c.*801A>T		3_prime_UTR	Exon 17 of 17	NP_001188331.1	P54803-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALC	ENST00000261304.7	TSL:1 MANE Select	c.*801A>T		3_prime_UTR	Exon 17 of 17	ENSP00000261304.2	P54803-1
	GALC	ENST00000921945.1		c.*801A>T		3_prime_UTR	Exon 16 of 16	ENSP00000592004.1
	GALC	ENST00000950382.1		c.*801A>T		3_prime_UTR	Exon 17 of 17	ENSP00000620441.1

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2115 AN: 152012 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00479

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00278 AC: 364 AN: 130770 AF XY: 0.00230

Gnomad AFR exome AF: 0.0491

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000200

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.00147 AC: 1907 AN: 1299278 Hom.: 53 Cov.: 20 AF XY: 0.00126 AC XY: 811 AN XY: 646004

African (AFR) AF: 0.0526 AC: 1565 AN: 29726

American (AMR) AF: 0.00225 AC: 80 AN: 35578

Ashkenazi Jewish (ASJ) AF: 0.0000406 AC: 1 AN: 24626

East Asian (EAS) AF: 0.00 AC: 0 AN: 35554

South Asian (SAS) AF: 0.000194 AC: 15 AN: 77482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33418

Middle Eastern (MID) AF: 0.00217 AC: 12 AN: 5534

European-Non Finnish (NFE) AF: 0.0000469 AC: 47 AN: 1002266

Other (OTH) AF: 0.00339 AC: 187 AN: 55094

GnomAD4 genome AF: 0.0140 AC: 2123 AN: 152130 Hom.: 47 Cov.: 33 AF XY: 0.0139 AC XY: 1037 AN XY: 74368

African (AFR) AF: 0.0483 AC: 2006 AN: 41516

American (AMR) AF: 0.00485 AC: 74 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68000

Other (OTH) AF: 0.0119 AC: 25 AN: 2108

Alfa AF: 0.00203 Hom.: 1

Bravo AF: 0.0166

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Galactosylceramide beta-galactosidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs114174103; hg19: chr14-88400275;