Genetic Variant GALT:c.-88G>A (chr9-34646617-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000450095.6(GALT):c.-290G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,554,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

GALT
ENST00000450095.6 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 1.83

Publications

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

GALT links:

ENSG00000294190 (HGNC:):

ENSG00000294190 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450095.6. 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
	GALT	NM_000155.4	MANE Select	c.-88G>A		upstream_gene	N/A	NP_000146.2
	GALT	NM_001258332.2		c.-290G>A		upstream_gene	N/A	NP_001245261.1	P07902-2

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
GALT	ENST00000902340.1	c.-88G>A	5_prime_UTR	Exon 1 of 10	ENSP00000572399.1
GALT	ENST00000902336.1	c.-88G>A	5_prime_UTR	Exon 1 of 11	ENSP00000572395.1
GALT	ENST00000902337.1	c.-88G>A	5_prime_UTR	Exon 1 of 10	ENSP00000572396.1

Frequencies

GnomAD3 genomes

AF:

0.000420

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.000512

AC:

718

AN:

1401646

Hom.:

Cov.:

AF XY:

0.000544

AC XY:

381

AN XY:

700464

show subpopulations

African (AFR)

AF:

0.0000311

AC:

AN:

32204

American (AMR)

AF:

0.000430

AC:

AN:

44224

Ashkenazi Jewish (ASJ)

AF:

0.00167

AC:

AN:

25716

East Asian (EAS)

AF:

0.00

AC:

AN:

39194

South Asian (SAS)

AF:

0.00

AC:

AN:

84790

European-Finnish (FIN)

AF:

0.0000966

AC:

AN:

51736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4332

European-Non Finnish (NFE)

AF:

0.000583

AC:

619

AN:

1061280

Other (OTH)

AF:

0.000533

AC:

AN:

58170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000420

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41592

American (AMR)

AF:

0.000392

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000617

AC:

AN:

68030

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000371

Hom.:

Bravo

AF:

0.000453

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase (1)

GALT-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

1.8

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over