chr9-34645848-A-ATTTTTTT

Position:

• chr9-34645848-A-ATTTTTTT

Variant summary

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

The ENST00000605275.1(GALT):​n.209-815_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 0.00079 (4 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-ATTTTTTT is Benign according to our data. Variant chr9-34645848-A-ATTTTTTT is described in ClinVar as [Benign]. Clinvar id is 1343439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000788 (99/125612) while in subpopulation SAS AF= 0.0107 (39/3650). AF 95% confidence interval is 0.00803. There are 4 homozygotes in gnomad4. There are 55 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALT	ENST00000605275.1	n.209-815_209-809dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000796 AC: 100 AN: 125634 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000492

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000236

Gnomad SAS AF: 0.0109

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00388

Gnomad NFE AF: 0.000114

Gnomad OTH AF: 0.000589

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

GnomAD4 genome AF: 0.000788 AC: 99 AN: 125612 Hom.: 4 Cov.: 0 AF XY: 0.000924 AC XY: 55 AN XY: 59556

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.000491

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000236

Gnomad4 SAS AF: 0.0107

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000114

Gnomad4 OTH AF: 0.000585

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

Feb 22, 2022

Variant summary: GALT c.-843_-837dupTTTTTTT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.00079 in 124530 control chromosomes in the gnomAD database (v3.1.2 dataset), including 4 homozygotes. The variant is predominantly found within the South Asian subpopulation at a frequency of 0.011. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 4-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. To our knowledge, no occurrence of c.-843_-837dupTTTTTTT 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

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;