9-34645685-CTTTTTTT-CTTTTTTTTT

Variant names:

• chr9-34645685-C-CTT
• rs201344398
• ENST00000605275.1:n.209-992_209-991insTT

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_209-991insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 137,514 control chromosomes in the GnomAD database, including 215 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.028 (215 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-CTT is Benign according to our data. Variant chr9-34645685-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1677034.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0921 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_209-991insTT		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1	n.127-1072_127-1071insAA		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 3791 AN: 137508 Hom.: 215 Cov.: 27

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00275

Gnomad EAS AF: 0.000417

Gnomad SAS AF: 0.00256

Gnomad FIN AF: 0.00114

Gnomad MID AF: 0.00699

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0223

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

GnomAD4 genome AF: 0.0276 AC: 3796 AN: 137514 Hom.: 215 Cov.: 27 AF XY: 0.0266 AC XY: 1765 AN XY: 66306

African (AFR) AF: 0.0947 AC: 3477 AN: 36704

American (AMR) AF: 0.0126 AC: 174 AN: 13762

Ashkenazi Jewish (ASJ) AF: 0.00275 AC: 9 AN: 3268

East Asian (EAS) AF: 0.000418 AC: 2 AN: 4780

South Asian (SAS) AF: 0.00257 AC: 11 AN: 4280

European-Finnish (FIN) AF: 0.00114 AC: 9 AN: 7914

Middle Eastern (MID) AF: 0.00379 AC: 1 AN: 264

European-Non Finnish (NFE) AF: 0.00113 AC: 72 AN: 63812

Other (OTH) AF: 0.0221 AC: 41 AN: 1854

Alfa AF: 0.00 Hom.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 08, 2022

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.-1005_-1004dupTT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.028 in 23774 control chromosomes, predominantly at a frequency of 0.09 within the African or African-American subpopulation in the gnomAD database, including 44 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 31.18 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 a benign polymorphism found primarily in populations of African or African-American origin.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;