9-34645848-A-ATTT

Variant names:

• chr9-34645848-A-ATTT
• rs549043849
• ENST00000605275.1:n.209-829_209-828insTTT

Variant summary

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

The ENST00000605275.1(GALT):​n.209-829_209-828insTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (3972 hom., cov: 0)
• Consequence: GALT ENST00000605275.1 intron
• 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-ATTT is Benign according to our data. Variant chr9-34645848-A-ATTT is described in ClinVar as [Benign]. Clinvar id is 1331424.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.302 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.209-829_209-828insTTT		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.241 AC: 30160 AN: 125386 Hom.: 3970 Cov.: 0

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.233

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.241 AC: 30157 AN: 125368 Hom.: 3972 Cov.: 0 AF XY: 0.237 AC XY: 14102 AN XY: 59420

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.0632

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.246

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 16, 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.-839_-837dupTTT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.24 in 124282 control chromosomes in the gnomAD v3.1.2 database, including 3940 homozygotes. The observed variant frequency is approximately 83-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. To our knowledge, no occurrence of c.-839_-837dupTTT 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;