9-34646057-AAG-A

Position:

• chr9-34646057-AAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000605275.1(GALT):​n.209-603_209-602del variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALT	ENST00000605275.1	n.209-603_209-602del		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0598

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0314

Gnomad4 OTH AF: 0.0354

Bravo AF: 0.0234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Dec 20, 2021

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149007102; hg19: chr9-34646054;