rs2277202

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000155.4(GALT):c.507+62G>A 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 1,614,130 control chromosomes in the GnomAD database, including 3,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.047 ( 261 hom., cov: 32)

Exomes 𝑓: 0.061 ( 2930 hom. )

Consequence

GALT
NM_000155.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 1.34

Publications

20 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALT	NM_000155.4 link	c.507+62G>A		intron_variant	Intron 5 of 10	ENST00000378842.8	NP_000146.2
GALT	NM_001258332.2 link	c.180+62G>A		intron_variant	Intron 3 of 8		NP_001245261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALT	ENST00000378842.8 link	c.507+62G>A		intron_variant	Intron 5 of 10	1	NM_000155.4	ENSP00000368119.4
ENSG00000258728	ENST00000556278.1 link	c.253-92G>A		intron_variant	Intron 2 of 7	5		ENSP00000451792.1

Frequencies

GnomAD3 genomes

AF:

0.0469

AC:

7133

AN:

152148

Hom.:

260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0486

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.00924

Gnomad SAS

AF:

0.0690

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0642

Gnomad OTH

AF:

0.0435

GnomAD4 exome

AF:

0.0613

AC:

89596

AN:

1461864

Hom.:

2930

Cov.:

AF XY:

0.0618

AC XY:

44974

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0103

AC:

345

AN:

33480

American (AMR)

AF:

0.0480

AC:

2145

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0512

AC:

1338

AN:

26136

East Asian (EAS)

AF:

0.00647

AC:

257

AN:

39700

South Asian (SAS)

AF:

0.0755

AC:

6511

AN:

86250

European-Finnish (FIN)

AF:

0.0678

AC:

3622

AN:

53412

Middle Eastern (MID)

AF:

0.0465

AC:

268

AN:

5768

European-Non Finnish (NFE)

AF:

0.0644

AC:

71596

AN:

1112000

Other (OTH)

AF:

0.0582

AC:

3514

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

5875

11749

17624

23498

29373

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:

7135

AN:

152266

Hom.:

261

Cov.:

AF XY:

0.0467

AC XY:

3476

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0122

AC:

509

AN:

41558

American (AMR)

AF:

0.0487

AC:

744

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

167

AN:

3470

East Asian (EAS)

AF:

0.00907

AC:

AN:

5180

South Asian (SAS)

AF:

0.0689

AC:

332

AN:

4822

European-Finnish (FIN)

AF:

0.0673

AC:

714

AN:

10608

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0642

AC:

4368

AN:

68022

Other (OTH)

AF:

0.0440

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

359

718

1078

1437

1796

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.:

344

Bravo

AF:

0.0421

Asia WGS

AF:

0.0340

AC:

118

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Benign:2Other:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Jul 06, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

7.2

(source)

DANN

Benign

0.70

PhyloP100

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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