Genetic Variant GALT:n.209-829_209-828insT (chr9-34645848-A-AT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000605275.1(GALT):n.209-829_209-828insT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.038 ( 112 hom., cov: 0)

Consequence

GALT
ENST00000605275.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.901

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: Labcorp Genetics (formerly Invitae), G2P, Orphanet
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: Benign. The variant received -10 ACMG points.

BP6

Variant 9-34645848-A-AT is Benign according to our data. Variant chr9-34645848-A-AT is described in ClinVar as [Benign]. Clinvar id is 1331458.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0381 (4788/125562) while in subpopulation NFE AF = 0.0431 (2645/61346). AF 95% confidence interval is 0.0417. There are 112 homozygotes in GnomAd4. There are 2258 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 112 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALT	ENST00000605275.1 link	n.209-829_209-828insT		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1 link	n.127-1235_127-1234insA		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0381

AC:

4788

AN:

125584

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.00591

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.0437

Gnomad EAS

AF:

0.00377

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0497

Gnomad MID

AF:

0.0271

Gnomad NFE

AF:

0.0431

Gnomad OTH

AF:

0.0347

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0381

AC:

4788

AN:

125562

Hom.:

112

Cov.:

AF XY:

0.0379

AC XY:

2258

AN XY:

59532

show subpopulations

African (AFR)

AF:

0.0395

AC:

1266

AN:

32036

American (AMR)

AF:

0.0246

AC:

300

AN:

12206

Ashkenazi Jewish (ASJ)

AF:

0.0437

AC:

141

AN:

3226

East Asian (EAS)

AF:

0.00378

AC:

AN:

4230

South Asian (SAS)

AF:

0.0129

AC:

AN:

3656

European-Finnish (FIN)

AF:

0.0497

AC:

302

AN:

6072

Middle Eastern (MID)

AF:

0.0297

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0431

AC:

2645

AN:

61346

Other (OTH)

AF:

0.0345

AC:

AN:

1708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

206

411

617

822

1028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0209

Hom.:

247

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 20, 2021

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: GALT c.-837dupT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.04 in 19482 control chromosomes in the gnomAD database, including 31 homozygotes. The observed variant frequency is approximately 13.73 fold of the estimated maximal expected allele frequency for a pathogenic variant in GALT causing Galactosemia phenotype (0.0029), strongly suggesting that the variant is benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr9-34645848-A-AT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over