9-34645848-A-ATTTTT

Variant names:

• chr9-34645848-A-ATTTTT
• rs549043849
• ENST00000605275.1:n.209-829_209-828insTTTTT

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_209-828insTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1825 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-ATTTTT is Benign according to our data. Variant chr9-34645848-A-ATTTTT is described in ClinVar as [Benign]. Clinvar id is 1331422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 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_209-828insTTTTT		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1	n.127-1235_127-1234insAAAAA		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 19948 AN: 125292 Hom.: 1828 Cov.: 0

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.159 AC: 19931 AN: 125268 Hom.: 1825 Cov.: 0 AF XY: 0.156 AC XY: 9253 AN XY: 59382

African (AFR) AF: 0.155 AC: 4945 AN: 31964

American (AMR) AF: 0.197 AC: 2386 AN: 12134

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 417 AN: 3226

East Asian (EAS) AF: 0.285 AC: 1199 AN: 4212

South Asian (SAS) AF: 0.142 AC: 519 AN: 3650

European-Finnish (FIN) AF: 0.0836 AC: 506 AN: 6050

Middle Eastern (MID) AF: 0.153 AC: 36 AN: 236

European-Non Finnish (NFE) AF: 0.155 AC: 9501 AN: 61250

Other (OTH) AF: 0.166 AC: 282 AN: 1700

Alfa AF: 0.0595 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.-841_-837dupTTTTT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.16 in 124188 control chromosomes in the gnomAD v3.1.2 database, including 1810 homozygotes. The observed variant frequency is approximately 55-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. 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;