9-34646343-G-T

Position:

• chr9-34646343-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000605275.1(GALT):​n.209-334G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 152,312 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.028 (101 hom., cov: 32)
• Consequence: GALT ENST00000605275.1 intron, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.171

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-34646343-G-T is Benign according to our data. Variant chr9-34646343-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALT	ENST00000605275.1	n.209-334G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4253 AN: 152194 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0279 AC: 4251 AN: 152312 Hom.: 101 Cov.: 32 AF XY: 0.0292 AC XY: 2178 AN XY: 74486

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0427

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0279 Hom.: 8

Bravo AF: 0.0234

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12551313; hg19: chr9-34646340;