14-87965554-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000153.4(GALC):c.984G>A(p.Gln328Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,612,286 control chromosomes in the GnomAD database, including 108,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8463 hom., cov: 32)

Exomes 𝑓: 0.36 ( 100131 hom. )

Consequence

GALC
NM_000153.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.68

Publications

36 publications found

Variant links:

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

GALC links:

LOC124903355 (HGNC:):

LOC124903355 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 14-87965554-C-T is Benign according to our data. Variant chr14-87965554-C-T is described in ClinVar as [Benign]. Clinvar id is 92513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4 link	c.984G>A	p.Gln328Gln	synonymous_variant	Exon 9 of 17	ENST00000261304.7	NP_000144.2	P54803-1A0A0A0MQV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 link	c.984G>A	p.Gln328Gln	synonymous_variant	Exon 9 of 17	1	NM_000153.4	ENSP00000261304.2		P54803-1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46761

AN:

151784

Hom.:

8463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.326

GnomAD2 exomes

AF:

0.390

AC:

97013

AN:

248956

AF XY:

0.392

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.519

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.338

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.364

AC:

531419

AN:

1460384

Hom.:

100131

Cov.:

AF XY:

0.366

AC XY:

265909

AN XY:

726546

show subpopulations

African (AFR)

AF:

0.113

AC:

3786

AN:

33440

American (AMR)

AF:

0.507

AC:

22622

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

9856

AN:

26082

East Asian (EAS)

AF:

0.612

AC:

24257

AN:

39668

South Asian (SAS)

AF:

0.429

AC:

37019

AN:

86232

European-Finnish (FIN)

AF:

0.343

AC:

18299

AN:

53404

Middle Eastern (MID)

AF:

0.371

AC:

2137

AN:

5758

European-Non Finnish (NFE)

AF:

0.353

AC:

391676

AN:

1110830

Other (OTH)

AF:

0.361

AC:

21767

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

17241

34482

51723

68964

86205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.308

AC:

46763

AN:

151902

Hom.:

8463

Cov.:

AF XY:

0.314

AC XY:

23324

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.125

AC:

5170

AN:

41498

American (AMR)

AF:

0.438

AC:

6667

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

1285

AN:

3472

East Asian (EAS)

AF:

0.582

AC:

2988

AN:

5138

South Asian (SAS)

AF:

0.413

AC:

1994

AN:

4824

European-Finnish (FIN)

AF:

0.346

AC:

3644

AN:

10540

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.352

AC:

23900

AN:

67912

Other (OTH)

AF:

0.324

AC:

681

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1508

3015

4523

6030

7538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.346

Hom.:

18733

Bravo

AF:

0.310

Asia WGS

AF:

0.408

AC:

1420

AN:

3478

EpiCase

AF:

0.367

EpiControl

AF:

0.371

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency

Benign:5

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nov 19, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 03, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

6.8

(source)

DANN

Benign

0.77

PhyloP100

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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14-87965554-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over