9-34646057-AAG-A

Variant names:

• chr9-34646057-AAG-A
• rs149007102
• ENST00000605275.1:n.209-619_209-618delAG

Variant summary

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

The ENST00000605275.1(GALT):​n.209-619_209-618delAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 149,316 control chromosomes in the GnomAD database, including 97 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.028 (97 hom., cov: 31)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250
• 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 9-34646057-AAG-A is Benign according to our data. Variant chr9-34646057-AAG-A is described in ClinVar as [Benign]. Clinvar id is 1331459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0946 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.209-619_209-618delAG		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1	n.127-1445_127-1444delCT		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4226 AN: 149236 Hom.: 98 Cov.: 31

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0598

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.0357

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

GnomAD4 genome AF: 0.0283 AC: 4224 AN: 149316 Hom.: 97 Cov.: 31 AF XY: 0.0296 AC XY: 2155 AN XY: 72806

African (AFR) AF: 0.0118 AC: 483 AN: 40880

American (AMR) AF: 0.0229 AC: 343 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.0598 AC: 206 AN: 3442

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5130

South Asian (SAS) AF: 0.102 AC: 482 AN: 4720

European-Finnish (FIN) AF: 0.0461 AC: 453 AN: 9836

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0314 AC: 2106 AN: 67118

Other (OTH) AF: 0.0354 AC: 72 AN: 2034

Alfa AF: 0.00755 Hom.: 0

Bravo AF: 0.0234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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.-631_-630delAG is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.027 in 28816 control chromosomes in the gnomAD database, including 10 homozygotes. The observed variant frequency is approximately 9.42 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		-0.025

Splicing

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

Other links and lift over

dbSNP: rs149007102; hg19: chr9-34646054;