9-34645848-A-ATTTT

Variant names:

• chr9-34645848-A-ATTTT
• rs549043849
• ENST00000605275.1:n.209-829_209-828insTTTT

Variant summary

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

The ENST00000605275.1(GALT):​n.209-829_209-828insTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.047 (296 hom., cov: 0)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.901
• 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 9-34645848-A-ATTTT is Benign according to our data. Variant chr9-34645848-A-ATTTT is described in ClinVar as [Benign]. Clinvar id is 1331426.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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.209-829_209-828insTTTT		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1	n.127-1235_127-1234insAAAA		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 5864 AN: 125572 Hom.: 296 Cov.: 0

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0865

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.00620

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.0116

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0371

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

GnomAD4 genome AF: 0.0467 AC: 5861 AN: 125550 Hom.: 296 Cov.: 0 AF XY: 0.0478 AC XY: 2843 AN XY: 59516

African (AFR) AF: 0.104 AC: 3328 AN: 32020

American (AMR) AF: 0.0552 AC: 673 AN: 12202

Ashkenazi Jewish (ASJ) AF: 0.00620 AC: 20 AN: 3228

East Asian (EAS) AF: 0.0629 AC: 266 AN: 4228

South Asian (SAS) AF: 0.0203 AC: 74 AN: 3654

European-Finnish (FIN) AF: 0.0357 AC: 217 AN: 6070

Middle Eastern (MID) AF: 0.0127 AC: 3 AN: 236

European-Non Finnish (NFE) AF: 0.0186 AC: 1144 AN: 61362

Other (OTH) AF: 0.0369 AC: 63 AN: 1706

Alfa AF: 0.0184 Hom.: 247

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.-840_-837dupTTTT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.047 in 19482 control chromosomes in the gnomAD database, including 45 homozygotes. The observed variant frequency is approximately 16.45 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.-840_-837dupTTTT 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		-0.90

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;