rs41274865

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000155.4(GALT):c.378-27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,614,114 control chromosomes in the GnomAD database, including 3,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.047 ( 261 hom., cov: 32)

Exomes 𝑓: 0.061 ( 2932 hom. )

Consequence

GALT
NM_000155.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 1.55

Publications

18 publications found

Variant links:

Genes affected

GALT (HGNC:4135): (galactose-1-phosphate uridylyltransferase) Galactose-1-phosphate uridyl transferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, namely the conversion of UDP-glucose + galactose-1-phosphate to glucose-1-phosphate + UDP-galactose. The absence of this enzyme results in classic galactosemia in humans and can be fatal in the newborn period if lactose is not removed from the diet. The pathophysiology of galactosemia has not been clearly defined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

GALT Gene-Disease associations (from GenCC):

classic galactosemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
galactosemia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health

GALT links:

ENSG00000258728 (HGNC:):

ENSG00000258728 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-34647805-G-C is Benign according to our data. Variant chr9-34647805-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 25166.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALT	NM_000155.4 link	c.378-27G>C		intron_variant	Intron 4 of 10	ENST00000378842.8	NP_000146.2	P07902-1B2RAT6A0A0S2Z3Y7
GALT	NM_001258332.2 link	c.51-27G>C		intron_variant	Intron 2 of 8		NP_001245261.1	P07902-2B2RAT6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALT	ENST00000378842.8 link	c.378-27G>C		intron_variant	Intron 4 of 10	1	NM_000155.4	ENSP00000368119.4		P07902-1
ENSG00000258728	ENST00000556278.1 link	c.253-310G>C		intron_variant	Intron 2 of 7	5		ENSP00000451792.1		G3V4G9

Frequencies

GnomAD3 genomes

AF:

0.0469

AC:

7137

AN:

152136

Hom.:

260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0488

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.00946

Gnomad SAS

AF:

0.0687

Gnomad FIN

AF:

0.0672

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0642

Gnomad OTH

AF:

0.0441

GnomAD2 exomes

AF:

0.0543

AC:

13652

AN:

251492

AF XY:

0.0565

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.0473

Gnomad ASJ exome

AF:

0.0512

Gnomad EAS exome

AF:

0.00870

Gnomad FIN exome

AF:

0.0687

Gnomad NFE exome

AF:

0.0613

Gnomad OTH exome

AF:

0.0599

GnomAD4 exome

AF:

0.0613

AC:

89600

AN:

1461860

Hom.:

2932

Cov.:

AF XY:

0.0618

AC XY:

44978

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.0103

AC:

345

AN:

33478

American (AMR)

AF:

0.0481

AC:

2149

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0512

AC:

1338

AN:

26136

East Asian (EAS)

AF:

0.00645

AC:

256

AN:

39700

South Asian (SAS)

AF:

0.0755

AC:

6512

AN:

86258

European-Finnish (FIN)

AF:

0.0678

AC:

3624

AN:

53420

Middle Eastern (MID)

AF:

0.0465

AC:

268

AN:

5768

European-Non Finnish (NFE)

AF:

0.0644

AC:

71594

AN:

1111982

Other (OTH)

AF:

0.0582

AC:

3514

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

5689

11378

17066

22755

28444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2650

5300

7950

10600

13250

<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:

0.0469

AC:

7139

AN:

152254

Hom.:

261

Cov.:

AF XY:

0.0467

AC XY:

3475

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0123

AC:

510

AN:

41554

American (AMR)

AF:

0.0488

AC:

747

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

167

AN:

3472

East Asian (EAS)

AF:

0.00928

AC:

AN:

5170

South Asian (SAS)

AF:

0.0685

AC:

330

AN:

4816

European-Finnish (FIN)

AF:

0.0672

AC:

713

AN:

10610

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0642

AC:

4369

AN:

68020

Other (OTH)

AF:

0.0445

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

352

704

1057

1409

1761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0549

Hom.:

Bravo

AF:

0.0421

Asia WGS

AF:

0.0340

AC:

118

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Benign:4Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 06, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Galactosemia

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.5

(source)

DANN

Benign

0.43

PhyloP100

1.6

BranchPoint Hunter

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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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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