9-34649053-G-A

Position:

chr9-34649053-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000155.4(GALT):c.876G>A(p.Thr292=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,614,048 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 154 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 186 hom. )

Consequence

GALT
NM_000155.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -3.28

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 9-34649053-G-A is Benign according to our data. Variant chr9-34649053-G-A is described in ClinVar as [Benign]. Clinvar id is 36158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALT	NM_000155.4 linkuse as main transcript	c.876G>A	p.Thr292=	synonymous_variant	9/11	ENST00000378842.8
GALT	NM_001258332.2 linkuse as main transcript	c.549G>A	p.Thr183=	synonymous_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALT	ENST00000378842.8 linkuse as main transcript	c.876G>A	p.Thr292=	synonymous_variant	9/11	1	NM_000155.4	P1	P07902-1

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

3949

AN:

152084

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00982

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00738

AC:

1855

AN:

251492

Hom.:

AF XY:

0.00572

AC XY:

778

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0912

Gnomad AMR exome

AF:

0.00468

Gnomad ASJ exome

AF:

0.00883

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.00537

GnomAD4 exome

AF:

0.00329

AC:

4808

AN:

1461846

Hom.:

186

Cov.:

AF XY:

0.00290

AC XY:

2110

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0933

Gnomad4 AMR exome

AF:

0.00514

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000540

Gnomad4 OTH exome

AF:

0.00820

GnomAD4 genome

AF:

0.0260

AC:

3955

AN:

152202

Hom.:

154

Cov.:

AF XY:

0.0251

AC XY:

1871

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0877

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.00982

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00842

Hom.:

Bravo

AF:

0.0302

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Benign:5

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing;curation	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 14, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 08, 2021	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Galactosemia

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

May 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.5

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over