9-34645848-A-ATT

Variant names:

• chr9-34645848-A-ATT
• rs549043849
• ENST00000605275.1:n.209-829_209-828insTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency: Genomes: 𝑓 0.065 (385 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-A-ATT is Benign according to our data. Variant chr9-34645848-A-ATT is described in ClinVar as [Benign]. Clinvar id is 1331397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0788 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	n.209-829_209-828insTT		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1	n.127-1235_127-1234insAA		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0648 AC: 8138 AN: 125558 Hom.: 383 Cov.: 0

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.00825

Gnomad SAS AF: 0.0678

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0504

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0495

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

GnomAD4 genome AF: 0.0649 AC: 8147 AN: 125538 Hom.: 385 Cov.: 0 AF XY: 0.0641 AC XY: 3818 AN XY: 59522

African (AFR) AF: 0.0814 AC: 2606 AN: 32026

American (AMR) AF: 0.0533 AC: 650 AN: 12194

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 155 AN: 3224

East Asian (EAS) AF: 0.00828 AC: 35 AN: 4228

South Asian (SAS) AF: 0.0676 AC: 247 AN: 3654

European-Finnish (FIN) AF: 0.0609 AC: 370 AN: 6078

Middle Eastern (MID) AF: 0.0508 AC: 12 AN: 236

European-Non Finnish (NFE) AF: 0.0627 AC: 3848 AN: 61346

Other (OTH) AF: 0.0498 AC: 85 AN: 1708

Alfa AF: 0.0360 Hom.: 247

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 14, 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.-838_-837dupTT is located in the untranscribed region upstream of the GALT gene region. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.063 in 19482 control chromosomes, predominantly at a frequency of 0.08 within the African or African-American subpopulation in the gnomAD database, including 23 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 28 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.-838_-837dupTT 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

Other links and lift over

dbSNP: rs549043849; hg19: chr9-34645845;