9-34645685-C-CT

Variant names:

• chr9-34645685-C-CT
• rs201344398
• ENST00000605275.1:n.209-992_209-991insT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000605275.1(GALT):​n.209-992_209-991insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 137,474 control chromosomes in the GnomAD database, including 992 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (992 hom., cov: 27)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.520
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-34645685-C-CT is Benign according to our data. Variant chr9-34645685-C-CT is described in ClinVar as [Benign]. Clinvar id is 1331423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 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.209-992_209-991insT		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1	n.127-1072_127-1071insA		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 15258 AN: 137468 Hom.: 994 Cov.: 27

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.111 AC: 15257 AN: 137474 Hom.: 992 Cov.: 27 AF XY: 0.110 AC XY: 7265 AN XY: 66292

African (AFR) AF: 0.137 AC: 5029 AN: 36700

American (AMR) AF: 0.0856 AC: 1178 AN: 13758

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 404 AN: 3268

East Asian (EAS) AF: 0.0519 AC: 248 AN: 4780

South Asian (SAS) AF: 0.194 AC: 829 AN: 4274

European-Finnish (FIN) AF: 0.0911 AC: 720 AN: 7904

Middle Eastern (MID) AF: 0.117 AC: 31 AN: 264

European-Non Finnish (NFE) AF: 0.101 AC: 6425 AN: 63792

Other (OTH) AF: 0.105 AC: 196 AN: 1858

Alfa AF: 0.0256 Hom.: 33

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.-1004dupT is located in the untranscribed region upstream of the GALT gene. The variant allele was found at a frequency of 0.1 in 23774 control chromosomes in the gnomAD database, including 156 homozygotes. The observed variant frequency is approximately 36-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.-1004dupT 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

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.52

Splicing

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

Other links and lift over

dbSNP: rs201344398; hg19: chr9-34645682;