chr9-34645848-A-ATTTTT

Position:

• chr9-34645848-A-ATTTTT

Variant summary

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

The ENST00000605275.1(GALT):​n.209-813_209-809dup variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1825 hom., cov: 0)
• Consequence: GALT ENST00000605275.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.901

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 9-34645848-A-ATTTTT is Benign according to our data. Variant chr9-34645848-A-ATTTTT is described in ClinVar as [Benign]. Clinvar id is 1331422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 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.209-813_209-809dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 19948 AN: 125292 Hom.: 1828 Cov.: 0

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.159 AC: 19931 AN: 125268 Hom.: 1825 Cov.: 0 AF XY: 0.156 AC XY: 9253 AN XY: 59382

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.166

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 16, 2021

Variant summary: GALT c.-841_-837dupTTTTT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.16 in 124188 control chromosomes in the gnomAD v3.1.2 database, including 1810 homozygotes. The observed variant frequency is approximately 55-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: rs549043849; hg19: chr9-34645845;