rs367327

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000153.4(GALC):c.1620A>G(p.Thr540Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,609,970 control chromosomes in the GnomAD database, including 791,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70143 hom., cov: 31)

Exomes 𝑓: 0.99 ( 720877 hom. )

Consequence

GALC
NM_000153.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.81

Publications

22 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 14-87945603-T-C is Benign according to our data. Variant chr14-87945603-T-C is described in ClinVar as Benign. ClinVar VariationId is 167118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4 link	c.1620A>G	p.Thr540Thr	synonymous_variant	Exon 14 of 17	ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 link	c.1620A>G	p.Thr540Thr	synonymous_variant	Exon 14 of 17	1	NM_000153.4	ENSP00000261304.2

Frequencies

GnomAD3 genomes

AF:

0.959

AC:

145664

AN:

151938

Hom.:

70104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.866

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

0.938

Gnomad SAS

AF:

0.994

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.964

GnomAD2 exomes

AF:

0.985

AC:

245232

AN:

248934

AF XY:

0.988

show subpopulations

Gnomad AFR exome

AF:

0.863

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

0.998

Gnomad EAS exome

AF:

0.939

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

AF:

0.994

AC:

1449420

AN:

1457914

Hom.:

720877

Cov.:

AF XY:

0.995

AC XY:

721779

AN XY:

725526

show subpopulations

African (AFR)

AF:

0.859

AC:

28614

AN:

33312

American (AMR)

AF:

0.991

AC:

44248

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

26013

AN:

26058

East Asian (EAS)

AF:

0.953

AC:

37815

AN:

39674

South Asian (SAS)

AF:

0.997

AC:

85980

AN:

86198

European-Finnish (FIN)

AF:

1.00

AC:

53390

AN:

53390

Middle Eastern (MID)

AF:

0.991

AC:

5701

AN:

5754

European-Non Finnish (NFE)

AF:

1.00

AC:

1108306

AN:

1108700

Other (OTH)

AF:

0.986

AC:

59353

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

426

852

1278

1704

2130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21588

43176

64764

86352

107940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.959

AC:

145763

AN:

152056

Hom.:

70143

Cov.:

AF XY:

0.960

AC XY:

71334

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.866

AC:

35927

AN:

41492

American (AMR)

AF:

0.984

AC:

15007

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

3465

AN:

3472

East Asian (EAS)

AF:

0.938

AC:

4817

AN:

5136

South Asian (SAS)

AF:

0.995

AC:

4797

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67884

AN:

67944

Other (OTH)

AF:

0.965

AC:

2039

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

280

560

839

1119

1399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.985

Hom.:

101894

Bravo

AF:

0.952

Asia WGS

AF:

0.961

AC:

3342

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Oct 27, 2015

Eurofins Ntd Llc (ga)

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

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Galactosylceramide beta-galactosidase deficiency

Benign:3

Nov 16, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.36

(source)

DANN

Benign

0.30

PhyloP100

-2.8

Mutation Taster

=66/34

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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