rs111033756

Variant names:

• chr9-34648773-C-A
• rs111033756
• NM_000155.4:c.699C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000155.4(GALT):​c.699C>A​(p.Val233Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALT NM_000155.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.859
• 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

ENSG00000258728 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 9-34648773-C-A is Benign according to our data. Variant chr9-34648773-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3639687.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.859 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000155.4. 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.699C>A	p.Val233Val	synonymous	Exon 8 of 11	NP_000146.2
	GALT	NM_001258332.2		c.372C>A	p.Val124Val	synonymous	Exon 6 of 9	NP_001245261.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALT	ENST00000378842.8	TSL:1 MANE Select	c.699C>A	p.Val233Val	synonymous	Exon 8 of 11	ENSP00000368119.4
	ENSG00000258728	ENST00000556278.1	TSL:5	c.432+317C>A		intron	N/A	ENSP00000451792.1
	GALT	ENST00000450095.6	TSL:2	c.372C>A	p.Val124Val	synonymous	Exon 6 of 9	ENSP00000401956.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Benign:1

Feb 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	6.1
DANN	Benign	0.83
PhyloP100		0.86
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs111033756; hg19: chr9-34648770;