9-34646581-A-T

Variant names:

• chr9-34646581-A-T
• rs1366467657
• ENST00000605275.1:n.209-96A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000605275.1(GALT):​n.209-96A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000899 in 1,112,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.61
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALT	NM_000155.4	c.-124A>T		upstream_gene_variant		ENST00000378842.8	NP_000146.2
GALT	NM_001258332.2	c.-326A>T		upstream_gene_variant			NP_001245261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALT	ENST00000378842.8	c.-124A>T		upstream_gene_variant		1	NM_000155.4	ENSP00000368119.4
ENSG00000258728	ENST00000556278.1	c.-124A>T		upstream_gene_variant		5		ENSP00000451792.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.99e-7 AC: 1 AN: 1112224 Hom.: 0 Cov.: 15 AF XY: 0.00000176 AC XY: 1 AN XY: 566998

African (AFR) AF: 0.00 AC: 0 AN: 26286

American (AMR) AF: 0.00 AC: 0 AN: 40974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23688

East Asian (EAS) AF: 0.00 AC: 0 AN: 36676

South Asian (SAS) AF: 0.00 AC: 0 AN: 77696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3564

European-Non Finnish (NFE) AF: 0.00000124 AC: 1 AN: 803844

Other (OTH) AF: 0.00 AC: 0 AN: 48708

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.059
DANN	Benign	0.71
PhyloP100		-4.6
PromoterAI		-0.071	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1366467657; hg19: chr9-34646578;