rs61735984

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_000155.4(GALT):c.510C>A(p.Ile170Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,614,188 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 12 hom. )

Consequence

GALT
NM_000155.4 splice_region, synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: 1.86

Publications

3 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:

ENSG00000258728 (HGNC:):

ENSG00000258728 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BP6

Variant 9-34648117-C-A is Benign according to our data. Variant chr9-34648117-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 281074.

BP7

Synonymous conserved (PhyloP=1.87 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000155.4. 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.510C>A	p.Ile170Ile	splice_region synonymous	Exon 6 of 11	NP_000146.2
	GALT	NM_001258332.2		c.183C>A	p.Ile61Ile	splice_region synonymous	Exon 4 of 9	NP_001245261.1	P07902-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GALT	ENST00000378842.8	TSL:1 MANE Select	c.510C>A	p.Ile170Ile	splice_region synonymous	Exon 6 of 11	ENSP00000368119.4	P07902-1
ENSG00000258728	ENST00000556278.1	TSL:5	c.255C>A	p.Ile85Ile	splice_region synonymous	Exon 3 of 8	ENSP00000451792.1	G3V4G9
GALT	ENST00000902340.1		c.549C>A	p.Ile183Ile	splice_region synonymous	Exon 5 of 10	ENSP00000572399.1

Frequencies

GnomAD3 genomes

AF:

0.00280

AC:

426

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00354

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00295

AC:

741

AN:

251494

AF XY:

0.00291

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.00359

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00323

AC:

4725

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00319

AC XY:

2317

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33480

American (AMR)

AF:

0.00136

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0120

AC:

641

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00347

AC:

3862

AN:

1112006

Other (OTH)

AF:

0.00252

AC:

152

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

311

622

934

1245

1556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.00280

AC:

426

AN:

152302

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41570

American (AMR)

AF:

0.000915

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0131

AC:

139

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00354

AC:

241

AN:

68020

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00283

Hom.:

Bravo

AF:

0.00195

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00294

EpiControl

AF:

0.00421

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase (2)

not provided (2)

Galactosemia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.9

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over