Genetic Variant ENST00000605275.1:n.209-829_209-828insTTT (chr9-34645848-A-ATTT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Frequency

Genomes: 𝑓 0.24 ( 3972 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-ATTT is Benign according to our data. Variant chr9-34645848-A-ATTT is described in ClinVar as [Benign]. Clinvar id is 1331424.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

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_209-828insTTT		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1 link	n.127-1235_127-1234insAAA		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

30160

AN:

125386

Hom.:

3970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.0632

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.233

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.247

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

GnomAD4 genome

AF:

0.241

AC:

30157

AN:

125368

Hom.:

3972

Cov.:

AF XY:

0.237

AC XY:

14102

AN XY:

59420

show subpopulations

African (AFR)

AF:

0.239

AC:

7651

AN:

31974

American (AMR)

AF:

0.231

AC:

2812

AN:

12176

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

917

AN:

3226

East Asian (EAS)

AF:

0.0632

AC:

267

AN:

4226

South Asian (SAS)

AF:

0.317

AC:

1156

AN:

3650

European-Finnish (FIN)

AF:

0.190

AC:

1151

AN:

6060

Middle Eastern (MID)

AF:

0.233

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.253

AC:

15522

AN:

61268

Other (OTH)

AF:

0.246

AC:

419

AN:

1706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

989

1979

2968

3958

4947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.160

Hom.:

247

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 16, 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.-839_-837dupTTT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.24 in 124282 control chromosomes in the gnomAD v3.1.2 database, including 3940 homozygotes. The observed variant frequency is approximately 83-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. To our knowledge, no occurrence of c.-839_-837dupTTT in individuals affected with Galactosemia and no experimental evidence demonstrating its impact on protein function have been reported. 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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ENST00000605275.1:n.209-829_209-828insTTT

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