9-34645848-A-ATTTTTT

Variant names:

• chr9-34645848-A-ATTTTTT
• rs549043849
• ENST00000605275.1:n.209-829_209-828insTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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

• Frequency: Genomes: 𝑓 0.010 (28 hom., cov: 0)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.901

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-34645848-A-ATTTTTT is Benign according to our data. Variant chr9-34645848-A-ATTTTTT is described in ClinVar as [Benign]. Clinvar id is 1677032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1287/125576) while in subpopulation AFR AF= 0.0223 (715/32026). AF 95% confidence interval is 0.021. There are 28 homozygotes in gnomad4. There are 637 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

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_209-828insTTTTTT		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1289 AN: 125598 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.0177

Gnomad AMR AF: 0.00729

Gnomad ASJ AF: 0.00899

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.000329

Gnomad MID AF: 0.00775

Gnomad NFE AF: 0.00446

Gnomad OTH AF: 0.00707

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

GnomAD4 genome AF: 0.0102 AC: 1287 AN: 125576 Hom.: 28 Cov.: 0 AF XY: 0.0107 AC XY: 637 AN XY: 59536

Gnomad4 AFR AF: 0.0223

Gnomad4 AMR AF: 0.00729

Gnomad4 ASJ AF: 0.00899

Gnomad4 EAS AF: 0.0194

Gnomad4 SAS AF: 0.0181

Gnomad4 FIN AF: 0.000329

Gnomad4 NFE AF: 0.00446

Gnomad4 OTH AF: 0.00761

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.-842_-837dupTTTTTT is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.0095 in 19482 control chromosomes, predominantly at a frequency of 0.021 within the African or African-American subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 7.27 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs549043849; hg19: chr9-34645845;