9-34645848-A-AT

Position:

• chr9-34645848-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000605275.1(GALT):​n.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 0.038 (112 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-AT is Benign according to our data. Variant chr9-34645848-A-AT is described in ClinVar as [Benign]. Clinvar id is 1331458.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0381 (4788/125562) while in subpopulation NFE AF= 0.0431 (2645/61346). AF 95% confidence interval is 0.0417. There are 112 homozygotes in gnomad4. There are 2258 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 112 AR gene

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.209-809dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 4788 AN: 125584 Hom.: 112 Cov.: 0

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.00591

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.0437

Gnomad EAS AF: 0.00377

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.0271

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0347

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

GnomAD4 genome AF: 0.0381 AC: 4788 AN: 125562 Hom.: 112 Cov.: 0 AF XY: 0.0379 AC XY: 2258 AN XY: 59532

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.0437

Gnomad4 EAS AF: 0.00378

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0497

Gnomad4 NFE AF: 0.0431

Gnomad4 OTH AF: 0.0345

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.-837dupT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.04 in 19482 control chromosomes in the gnomAD database, including 31 homozygotes. The observed variant frequency is approximately 13.73 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;