ENST00000605275.1:n.209-101_209-94delCAGTCAGT

Variant names:

• chr9-34646575-CCAGTCAGT-C
• rs111033640
• ENST00000605275.1:n.209-101_209-94delCAGTCAGT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000605275.1(GALT):​n.209-101_209-94delCAGTCAGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000939 in 1,065,102 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• galactosemia

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

ENSG00000294190 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000605275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALT	NM_000155.4	MANE Select	c.-129_-122delCAGTCAGT		upstream_gene	N/A	NP_000146.2
	GALT	NM_001258332.2		c.-331_-324delCAGTCAGT		upstream_gene	N/A	NP_001245261.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALT	ENST00000605275.1	TSL:3	n.209-101_209-94delCAGTCAGT		intron	N/A
	ENSG00000294190	ENST00000721802.1		n.127-1969_127-1962delACTGACTG		intron	N/A
	GALT	ENST00000378842.8	TSL:1 MANE Select	c.-129_-122delCAGTCAGT		upstream_gene	N/A	ENSP00000368119.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.39e-7 AC: 1 AN: 1065102 Hom.: 0 AF XY: 0.00000184 AC XY: 1 AN XY: 544704

African (AFR) AF: 0.00 AC: 0 AN: 25418

American (AMR) AF: 0.00 AC: 0 AN: 39784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23272

East Asian (EAS) AF: 0.00 AC: 0 AN: 36074

South Asian (SAS) AF: 0.00 AC: 0 AN: 76240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3434

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 763372

Other (OTH) AF: 0.00 AC: 0 AN: 47092

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26

Splicing

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

Other links and lift over

dbSNP: rs111033640; hg19: chr9-34646572;