ENST00000605275.1:n.209-828delT

Variant names:

• chr9-34645848-AT-A
• rs549043849
• ENST00000605275.1:n.209-828delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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

• Frequency: Genomes: 𝑓 0.0093 (19 hom., cov: 0)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.901
• Publications: 0 publications found

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

ENSG00000294190 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-34645848-AT-A is Benign according to our data. Variant chr9-34645848-AT-A is described in ClinVar as [Benign]. Clinvar id is 1331425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00933 (1172/125588) while in subpopulation AFR AF = 0.0301 (965/32036). AF 95% confidence interval is 0.0285. There are 19 homozygotes in GnomAd4. There are 562 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 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	n.209-828delT		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1	n.127-1235delA		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1168 AN: 125610 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.000310

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.000816

Gnomad FIN AF: 0.00872

Gnomad MID AF: 0.0116

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.00708

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

GnomAD4 genome AF: 0.00933 AC: 1172 AN: 125588 Hom.: 19 Cov.: 0 AF XY: 0.00944 AC XY: 562 AN XY: 59534

African (AFR) AF: 0.0301 AC: 965 AN: 32036

American (AMR) AF: 0.00491 AC: 60 AN: 12208

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 1 AN: 3228

East Asian (EAS) AF: 0.00118 AC: 5 AN: 4230

South Asian (SAS) AF: 0.000821 AC: 3 AN: 3656

European-Finnish (FIN) AF: 0.00872 AC: 53 AN: 6076

Middle Eastern (MID) AF: 0.00847 AC: 2 AN: 236

European-Non Finnish (NFE) AF: 0.00112 AC: 69 AN: 61366

Other (OTH) AF: 0.00821 AC: 14 AN: 1706

Alfa AF: 0.00 Hom.: 247

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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.-837delT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.0094 in 124506 control chromosomes, predominantly at a frequency of 0.03 within the African or African-American subpopulation in the gnomAD database, including 19 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 10-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 a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.-837delT 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
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs549043849; hg19: chr9-34645845;