rs41274865

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000155.4(GALT):c.378-27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,614,114 control chromosomes in the GnomAD database, including 3,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.047 ( 261 hom., cov: 32)

Exomes 𝑓: 0.061 ( 2932 hom. )

Consequence

GALT
NM_000155.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 1.55

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:

ENSG00000258728 (HGNC:):

ENSG00000258728 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-34647805-G-C is Benign according to our data. Variant chr9-34647805-G-C is described in ClinVar as [Benign]. Clinvar id is 25166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALT	NM_000155.4 link	c.378-27G>C		intron_variant	Intron 4 of 10	ENST00000378842.8	NP_000146.2	P07902-1B2RAT6A0A0S2Z3Y7
GALT	NM_001258332.2 link	c.51-27G>C		intron_variant	Intron 2 of 8		NP_001245261.1	P07902-2B2RAT6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALT	ENST00000378842.8 link	c.378-27G>C		intron_variant	Intron 4 of 10	1	NM_000155.4	ENSP00000368119.4		P07902-1
ENSG00000258728	ENST00000556278.1 link	c.253-310G>C		intron_variant	Intron 2 of 7	5		ENSP00000451792.1		G3V4G9

Frequencies

GnomAD3 genomes

AF:

0.0469

AC:

7137

AN:

152136

Hom.:

260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0488

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.00946

Gnomad SAS

AF:

0.0687

Gnomad FIN

AF:

0.0672

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0642

Gnomad OTH

AF:

0.0441

GnomAD3 exomes

AF:

0.0543

AC:

13652

AN:

251492

Hom.:

439

AF XY:

0.0565

AC XY:

7675

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.0473

Gnomad ASJ exome

AF:

0.0512

Gnomad EAS exome

AF:

0.00870

Gnomad SAS exome

AF:

0.0754

Gnomad FIN exome

AF:

0.0687

Gnomad NFE exome

AF:

0.0613

Gnomad OTH exome

AF:

0.0599

GnomAD4 exome

AF:

0.0613

AC:

89600

AN:

1461860

Hom.:

2932

Cov.:

AF XY:

0.0618

AC XY:

44978

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.0481

Gnomad4 ASJ exome

AF:

0.0512

Gnomad4 EAS exome

AF:

0.00645

Gnomad4 SAS exome

AF:

0.0755

Gnomad4 FIN exome

AF:

0.0678

Gnomad4 NFE exome

AF:

0.0644

Gnomad4 OTH exome

AF:

0.0582

GnomAD4 genome

AF:

0.0469

AC:

7139

AN:

152254

Hom.:

261

Cov.:

AF XY:

0.0467

AC XY:

3475

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0123

Gnomad4 AMR

AF:

0.0488

Gnomad4 ASJ

AF:

0.0481

Gnomad4 EAS

AF:

0.00928

Gnomad4 SAS

AF:

0.0685

Gnomad4 FIN

AF:

0.0672

Gnomad4 NFE

AF:

0.0642

Gnomad4 OTH

AF:

0.0445

Alfa

AF:

0.0549

Hom.:

Bravo

AF:

0.0421

Asia WGS

AF:

0.0340

AC:

118

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Benign:4Other:1

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Galactosemia

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.5

DANN

Benign

0.43

BranchPoint Hunter

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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