9-34645848-ATTTTTTTTTT-ATTTTTTT

Variant names:

• chr9-34645848-ATTT-A
• rs549043849
• ENST00000902330.1:c.-28-828_-28-826delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000902330.1(GALT):​c.-28-828_-28-826delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000040 (0 hom., cov: 0)
• Consequence: GALT ENST00000902330.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.179
• Publications: 0 publications found

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]

GALT Gene-Disease associations (from GenCC):

• classic galactosemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• galactosemia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health

ENSG00000294190 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000902330.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALT	ENST00000902330.1		c.-28-828_-28-826delTTT		intron	N/A	ENSP00000572389.1
	GALT	ENST00000902331.1		c.-28-828_-28-826delTTT		intron	N/A	ENSP00000572390.1
	GALT	ENST00000902333.1		c.-28-828_-28-826delTTT		intron	N/A	ENSP00000572392.1

Frequencies

GnomAD3 genomes AF: 0.0000398 AC: 5 AN: 125632 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000236

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000165

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000398 AC: 5 AN: 125632 Hom.: 0 Cov.: 0 AF XY: 0.0000504 AC XY: 3 AN XY: 59546

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000937 AC: 3 AN: 32018

American (AMR) AF: 0.00 AC: 0 AN: 12200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3228

East Asian (EAS) AF: 0.000236 AC: 1 AN: 4244

South Asian (SAS) AF: 0.00 AC: 0 AN: 3676

European-Finnish (FIN) AF: 0.000165 AC: 1 AN: 6076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61388

Other (OTH) AF: 0.00 AC: 0 AN: 1698

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0425762), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 247

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs549043849; hg19: chr9-34645845;