chr9-34647805-G-C

Variant names:

• chr9-34647805-G-C
• rs41274865
• NM_000155.4:c.378-27G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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 Conflicting classifications of pathogenicity (no stars). 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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 B:8 O:1
• Conservation: PhyloP100: 1.55
• Publications: 18 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

ENSG00000258728 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 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 Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 25166.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000155.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALT	NM_000155.4	MANE Select	c.378-27G>C		intron	N/A	NP_000146.2
	GALT	NM_001258332.2		c.51-27G>C		intron	N/A	NP_001245261.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALT	ENST00000378842.8	TSL:1 MANE Select	c.378-27G>C		intron	N/A	ENSP00000368119.4
	ENSG00000258728	ENST00000556278.1	TSL:5	c.253-310G>C		intron	N/A	ENSP00000451792.1
	GALT	ENST00000472111.5	TSL:2	n.607G>C		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7137 AN: 152136 Hom.: 260 Cov.: 32

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

GnomAD2 exomes AF: 0.0543 AC: 13652 AN: 251492 AF XY: 0.0565

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 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.: 33 AF XY: 0.0618 AC XY: 44978 AN XY: 727232

African (AFR) AF: 0.0103 AC: 345 AN: 33478

American (AMR) AF: 0.0481 AC: 2149 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0512 AC: 1338 AN: 26136

East Asian (EAS) AF: 0.00645 AC: 256 AN: 39700

South Asian (SAS) AF: 0.0755 AC: 6512 AN: 86258

European-Finnish (FIN) AF: 0.0678 AC: 3624 AN: 53420

Middle Eastern (MID) AF: 0.0465 AC: 268 AN: 5768

European-Non Finnish (NFE) AF: 0.0644 AC: 71594 AN: 1111982

Other (OTH) AF: 0.0582 AC: 3514 AN: 60394

GnomAD4 genome AF: 0.0469 AC: 7139 AN: 152254 Hom.: 261 Cov.: 32 AF XY: 0.0467 AC XY: 3475 AN XY: 74432

African (AFR) AF: 0.0123 AC: 510 AN: 41554

American (AMR) AF: 0.0488 AC: 747 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 167 AN: 3472

East Asian (EAS) AF: 0.00928 AC: 48 AN: 5170

South Asian (SAS) AF: 0.0685 AC: 330 AN: 4816

European-Finnish (FIN) AF: 0.0672 AC: 713 AN: 10610

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4369 AN: 68020

Other (OTH) AF: 0.0445 AC: 94 AN: 2110

Alfa AF: 0.0549 Hom.: 51

Bravo AF: 0.0421

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Benign:8 Other:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Pathogenic:1 Benign:4 Other:1

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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

Sep 10, 2025

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely pathogenic

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.43
PhyloP100		1.6
BranchPoint Hunter		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41274865; hg19: chr9-34647802; COSMIC: COSV66592691; COSMIC: COSV66592691;